Thursday, August 30, 2007

Another savage blow to my Behe critique

ERV, banned at UD for being *sarcastic*, aka repeatedly anticipating and demolishing Sallys attempts to move goal posts, and answering Davies attempts at being *mean* with cheer.

Have fun scissoring each other, pussies.

ROFL!

Poor Tweedle-Dee and Tweedle-Dumb, too stupid to know Behe was trying to let my post blow over. Trying sooooooo hard to ignore my post, hoping others would forget I wrote it... And then Dee and Dumb plaster it on the front page of UD and let me smash their Creationist Claims on their own damn blog!

AAAAAAAAHAHAHAHAHAHAHA! IDiots! AAAAAAAAHAHAHAHAHAHA!!!!

210 comments:

1 – 200 of 210   Newer›   Newest»
JoeyJoJoJr said...

Congrats on getting banned at UD! Guess that just shows us how Dave responds to a valid and sound argument. If you don't like the message, kill the messenger!

J-Dog said...

ERV - Please come visit the ATBC Uncommonly Dense Discussion thread for more fun bashing DaveTard and his minions.

http://www.antievolution.org/cgi-bin/ikonboard/ikonboard.cgi?s=46d6c83a35e98aee;act=ST;f=14;t=1274;st=18390

The Factician said...

Heh, I got banned, too. Not really sure why, but I have a hypothesis. I posted it here.

Salvador T. Cordova said...

Ms Smith,

This is Salvador Cordova from UD. I had nothting to do with your banning and I lobbied DaveScot to allow you to stay.

I was wondering if I could we could continue our dialogue. I only have a few more questions, and don't intend to trouble you much over them.

Salvador

Anonymous said...

Ooh, yes, please let Sal continue. He is about to deliver the coup de grace, don't you know.

Hey, Sal, since you seem to have insights not available to actual practitioners of biology, genetics, and virology you really should start your own biomedical research company based on the ID paradigm. I'll bet you could attract lots of funding and wouldn't it be a big splatter of egg on the Darwinists faces when you patented a breakthrough treatment.

The Factician said...

Waah!!!! The Darwinsits are gone. Sniff. They just couldn’t control themselves. Crying shame.

They couldn't control themselves? What did I do besides disagree with the other posters? I didn't even come out and say that they were wrong, I just said that their positions were highly improbable.

Couldn't control myself? Please, sir, you are being disingenuous. As Wesley says in The Princess Bride:

"We are men of action, lies do not become us."

Salvador T. Cordova said...

Annonymous said:
"since you seem to have insights not available to actual practitioners of biology,"

Not at all, I'm just a dumb uneducated dolt who has an overinflated view of himself, that's why I was hoping Ms. Smith could help me understand something.

I looked at the phylogeny that was suggested by Dr. Musgrave here:
Illustrated Guide to Vpu

Is it Ms. Smith's expert scientific opinion that Dr. Musgrave's diagram indicates that Vpu was present in HIV-1 strains when they were first introduced into the human population?

Anonymous said...

Not at all, I'm just a dumb uneducated dolt who has an overinflated view of himself, that's why I was hoping Ms. Smith could help me understand something.


Oh, so you aren't here to deliver the coup de grace like you said over at UD? I guess I should have realized that was just some good natured chest thumping for your homeys.

Do carry on.

Smokey said...

Um...Sal, if you're merely "hoping Ms. Smith could help me understand something," how do you explain your cowardly (only after the banning) boast on UD: "I was just about to deliver the coup de grace to all 3."

http://www.uncommondescent.com/darwinism/ervs-challenge-to-michael-behe/#comment-134816

Your dishonesty is truly breathtaking, as are your violent metaphorical fantasies about your debate opponents.

olegt said...

If there's a bright bulb at UD, it's DaveScot. He has finally figured out how damaging Abbie's presence could be to their cozy circle and moved in to cut losses. Three bans in one post! That'll show them Darwinists! LOL

Sal, how's the Young Earth doing? I hear you have started graduate school. Tell us where and in what field. We're dying to know.

art said...

Sal, perhaps you can explain this, um, massive revision of Behe's writing:

On UD, you said: This was the more interesting of the assertions offered as a counter example to Behe. But there is a subtle Equivocation in this statement that only make it appear Behe’s points were refuted when in fact they weren’t.

There are at least two notions of “protein-protein binding”:

1. protein-protein binding within the same organism upon which a critical function depends.

(i.e. see the bindings of a protein as function in Protein Dark Energy)

2. protein-protein binding between one organism’s protein (like HIV) to another organism’s protein (like human CD4)

Mike was referring to #1, and Ms. Smith to #2, therefore, because this is an equivocation, #2 cannot be used as a counter example to #1.


Behe, in contrast, spends a fair amount of time telling us how Darwinian mechanisms cannot allow Plasmodium to overcome resistance conferred by the sickle cell trait. All of this discussion is in the context of protein-protein interactions. In other words, Sal, Behe is talking exactly about interactions between proteins encoded by different genomes and organisms. What's with this - why do you need to alter Behe's words and ideas so radically? Did you think no one would notice?

DaveScot was wise to evict your critics - Behe has been soundly and thoroughly refuted by Abbie, and it's not good to have such developments displayed on Dembski's blog.

Salvador T. Cordova said...

Olegt said: "You have started graduate school. Tell us where and in what field. We're dying to know."


I'm learning the science of Denial and Deception from the University of Charles Darwin.

Ah, but I see Dr. Arthur Hunt of Pandas Thumb is here. YAY!

You know Art, I'd like to answer your question, but there is something I need a little help with first so I can understand where you're coming from.

When you read those phylogenies Dr. Musgrave offered, does that suggest to you that Vpu existed in HIV-1 strains prior to their introduction into humans?

I was hoping Ms. Smith could offer her expert opinion, but perhaps in the interim you could tell us what you think of Dr. Musgrave's phylogenies with respect to that questin.

Hermagoras said...

Sal in good-cop mode:

This is Salvador Cordova from UD. I had nothting [sic] to do with your banning and I lobbied DaveScot to allow you to stay.

How nice. Obviously you are a gentleman, as shown here:

Waah!!!! The Darwinsits [sic] are gone. Sniff. They just couldn’t control themselves. Crying shame.

Hypocrite, thy name is Sal.

Dave said...

Sal

Let me just add to the chorus of dismay at your sliminess, preening and boasting about the mythical coup de grace on UD only after your opponents were banned, and then parading your obsequiousness here. You are indeed unique. Thank god for that!

Oh, and if you ever get around to posting a real-world worked-through example of the Explanatory Filter on the SciPhi blog, please let us all know. Somehow your boasting over there seems to have the same endpoint as it will here. Zip, zilch, nada, nothing. Just like all the research output from those ID scientists who exist only in your tiny brain.

olegt said...

Sal, why don't you invite Michael Behe to appear on Abbie's blog. You are clearly not in a position to argue with her. If you are hesitant to write to him I can do so myself.

Hermagoras said...

Sal makes predictions. I can't predict the future. Hell, at UD you can't even tell the past, because they erase their history.

How about answering Art's question honestly? How about quitting the bullshit? How about not deleting posts at UD after they've appeared and pretending to know nothing about it (that's a question for your friend DaveScotSpringer).

Salvador T. Cordova said...

Well Oleg Tchernyshyov I'm in the unfortunate position of stuydying physics at your school, Johns Hopkins.

Do you look forward to dismissing me?

Salvador T. Cordova

olegt said...

Sal, you have nothing to worry. I deal with physics and only physics in my class (and so do my colleagues).

Why do you say your position is unfortunate? Johns Hopkins is a pretty good school as far as physics and astronomy is concerned. Are you studying part-time? I don't see you on the list of our incoming graduate students...

The Factician said...

Irony alert:

DaveScot: "You can’t reason with unreasonable people."

Does that sound like a confession to you?

art said...

Olegt,

FYI I asked Behe to review and comment on a Panda's Thumb essay I posted (entitled "Reality 1, Behe 0"). Behe declined, claiming that he did not want to be drawn into discussions on blogs.

So I doubt that he will pay you any heed. Behe, IMO, is every bit as keen to duck substantive debate as his acolytes on UD.

For good reason, as the discussion about Abbie's essay and work shows.

The Factician said...

Mr. Cordova,

Let me point you to the relevant portion of ERV's post--->

""Sure it's new in chimpanzees, but its not *new* in HIV-1!" Sorry, you'll find no escape with that limp-wristed, ad hoc parry. SIVcpz Vpu and HIV-1 Vpu act in different ways, biochemically , which is predictable enough when you do something as simple as comparing amino acid sequences. For instance, if you compare a laboratory strain gag to SIVcpz gag, you get a similarity of ~75%3. Not too shabby. On the other hand, if you compare the subunit portion of env (the gene I use to create phylogenetic trees because it's the most variable between viruses) you get an AA similarity of only ~59.5%."

Salvador T. Cordova said...

Olegt wrote: "Sal, you have nothing to worry. I deal with physics and only physics in my class (and so do my colleagues).

Why do you say your position is unfortunate? Johns Hopkins is a pretty good school as far as physics and astronomy is concerned. Are you studying part-time? I don't see you on the list of our incoming graduate students... "


Yes. I am studying through the Whiting School of Engineering, and only got my acceptance confirmed 2 days ago. I had considered studying under Dr. Robert Marks at Baylor at the informatics lab.

I had studied at Hopkins as an undergrad years ago before I ran out of money and went to GMU. I'm so glad to be back.

My apologies if I was disresptectful earlier Dr. Tchernyshyov as I did not know who you were until Bill Dembski copied on me an e-mail with your name.

I'm listed at Hopkins under the last name "Cordova", but you'll see me under my birth name, not under "Salvador".

I had my advising session with Dr. Allen Bjerkaas this past Tuesday, and my first class will be 615.465.31, Modern Physics under Dr. S. Hawkins.

I had not decided on a specialization, but I was interested in condensed matter physics.

respectfully,
Salvador Cordova

PS
You have my permission to confirm publicly whether I'm indeed enrolled. It will be under "cordova" but under my birthname which I don't disclose publicly.

The Factician said...

My apologies if I was disresptectful earlier Dr. Tchernyshyov as I did not know who you were

Does anyone know how to spell obsequious?

"I'm sorry I was rude earlier, I didn't know you would have power over my future."

*thunder in the distance*
*evil cackle*

Smokey said...

factician asked:
"Does anyone know how to spell obsequious?"

In Sal's case, C-O-W-A-R-D!

Sal, if you know you're right, in science you can challenge existing dogma, but you do so with data, not rhetoric.

Your cowardice just shows that your intent was always to deceive.

Smokey said...

Richardthughes had the best summary of Sal's weaseling:

I was going to score 2 goals and then the winner, but I took my ball home with me...

Dave said...

Does anyone know how to spell obsequious?

I think I spelled it in the traditional manner in my 11:46 comment above. But I agree with Smokey, the two-syllable version COWARD is probably more correct.

What a slimeball is our Sal.

PaV said...

ERV, this is PaV from UD.

I saw an answer to one of my questions, so, thank you.

From your answer I think you would agree that when HIV-1 appears, Vpu is already present.

Your argument then consists of the fact that (1) vpu in simians is different from humans, and, more importantly, they act in different biochemical manners. (2) there are different groups of HIV-1, and different subtypes. In, e.g., the B and C subtypes, we see different biochemical functions.

Have I summarized your argument well enough?

Oldcola said...

Banned at UD, welcome to the club lady ;-)
We should set-up a real club someday. With beer and stuff like that.
And maybe invite DaveScott for a conference :-D

Smokey said...

PaV,

I think that ERV's position is very clear from her PT post.

The question for you is, if Vpu from different HIV-1 subtypes has different functions, is Behe wrong because he wrote:

Yet through all that, there have been no significant basic biochemical changes in the virus at all.

????

steveh said...

Slimy: "I had considered studying under Dr. Robert Marks at Baylor at the informatics lab."

Last I heard there was no such thing -- just a guy there who writes about ID in his spare time, obtained a domain name, and pointed it to some pages he'd added under his own personal section of the university web site, purporting to be the web pages of a major Baylor Institution.

Baylor hadn't granted him permission to misuse their good name in this manner and quite rightly put an end to the deception.

Currently www.evolutionaryinformatics.org is parked at domain name provider, godaddy, until the domain owner finds another unwitting host.

The Factician said...

Baylor...their good name

Good name? Don't mistake Baylor University with Baylor College of Medicine. They're not affiliated, and Baylor University is a Baptist school. Dembski ought to be quite comfortable there.

Baylor College of Medicine is home to one of the larges sequencing centers and genetics departments in the U.S.

They used to be affiliated, but ended that affiliation in the 1950s.

Hermagoras said...

Dembski's no longer at Baylor. He's at Southwestern Baptist Seminary and Homemaking Academy

Hermagoras said...

Sal's inviting his UD friends to pester you until you answer his question about an alleged misreading.

You did say there were no stupid questions. (There are asinine questioners, as Sal amply proves.)

Smokey said...

Oh-oh...Sal's sliming Abbie over at UD now, trying his best to pretend that Behe didn't explicitly set a goal post at "no significant basic biochemical changes in the virus at all," but at 'no new genes in humans.'

I think Sal was lying when he claimed to want to continue his dialogue with Abbie.

steveh said...

"Good name? Don't mistake Baylor University with Baylor College of Medicine. They're not affiliated, and Baylor University is a Baptist school. Dembski ought to be quite comfortable there. "

I thought Demsbki had been ousted by the baptist university's athiest controllers. And "good name" is a relative term ;)

The Factician said...

Had to repost this from After the Bar Closes:

"Richardthughes

Cliffhanger recap from UD:

Last Episode

Sal had beaten ERV so hard they had to ban her before Sal delivered the coup de grace. Sal is now not going to go on her nixplanitary free blog because he might over slam-dunk his home run. He knows if he hits the bullseye, the rest of the dominos will fall like a house of cards. Checkmate!"

olegt said...

Sal,

I can't confirm your enrollment at JHU. For starters, I don't know your birth name. Furthermore, is a continuing education program and part-time students are not necessarily listed in the JHU directory, so your name may not even be there.

It's highly unlikely that our paths will ever cross: EPP courses in applied physics are taught by folks from the
Applied Physics Lab, a big R&D outfit for the government in Laurel, MD, not on the main campus in Baltimore.

Lastly, from your description I understand that you will be working on an M.S. with a possible concentration in materials and condensed matter. Not to nitpick, but I wouldn't call this graduate school since you won't be doing research and defending a thesis.

olegt said...

Heh, I messed up HTML code again. The second sentence should read: "Furthermore, EPP is a continuing education program..."

arthur Hunt said...

Hi PaV,

I posted an answer to some questions you asked me on the UD blog, and they were removed, possibly before you had a chance to think about them. I'm going to hijack Abbie's blog and post them here (like I have in another thread) on the chance that you may find the answers of interest. Enjoy.
---------------------------
PaV, two points for now. First, the paper about TASK-1 is interesting. I'm not sure if HIV actually captured the N-terminus of TASK-1 as proposed by these authors. I have some ideas, but I'd rather give Abbie an opportunity to comment on this study. Regardless, this still leaves several (four? - I have to go back and count 'em) "CCC"'s that arose after the fact, as it were.

Second, you said: Two things here: (1) what does the calculation look like wherein you arrive at these numbers; (2) in the case of T-urf-13, aren’t we dealing with: (a) mitochondrial plant DNA which, in the case of cms, is known to produce chimeric proteins, and (b) whose genetic mechanisms aren’t fully understood, and (c), in the case of ‘maize’, had to at some time been subjected to artificial selection, and therefore not a relevant comparison?

The calculations I cite were posted by Ian Musgrave in the comments to Abbie's essay (these pertain to VPu) and by myself in the essay I linked to above. Points (a) (at least the part about chimeric proteins) and (b) you mention are not relevant to T-urf13.

Point c has never made much sense to me. (Think about it. What is more "natural" - parasite populations evolving as a consequence of exposure to a man-made chemical, or a breeder choosing a trait known to occur in nature, via random genetic variation? Put another way, I always get the feeling when someone says as you do that they believe that breeders in the 50's and 60's in some way designed T-urf13 from first principles and then went in and deliberately manipulated the maize mt genome to place the T-urf13 gene there. This is, to be honest, patently ludicrous. Of course, maybe you have something else in mind. Feel free to elaborate.)
------------------------
Thanks to Abbie for her patience with my re-posts.

Salvador T. Cordova said...

smokey wrote: "I think Sal was lying when he claimed to want to continue his dialogue with Abbie."

We can continue the dialogue. I invited the readers to visit here to hear Ms. Smith's case. Because she is banned this is the most that I can do.

I would hope Ms. Smith will articulate the details of what she believes Musgrave's phylogeny says and what the peer-reviewed papers say.

The first question I posed was, "did HIV-1 have Vpu when it entered humans?"

A simple "yes", "no", or "I don't know" would suffice.

Hermagoras here has fiercly criticized me.

But what is his answer to that question? How does he think Ms. Smith will respond?

How about Dr. Hunt? What is his answer to this simple question?

How about anyone else who has labeled me a liar? What is your answer to the question?

When Ms. Smith articulates her position on the matter, then we can proceed as that question is fairly central to this discussion.

PaV said...

Smokey wrote:
The question for you is, if Vpu from different HIV-1 subtypes has different functions, is Behe wrong because he wrote:

"Yet through all that, there have been no significant basic biochemical changes in the virus at all."


I don't think Behe wrote what you've quoted. Do you know where this quote is supposed to be from?

Behe did write this (p. 140):

"Nonetheless, despite the many differences between [HIV and the malarial parasite], the evolutionary changes in both in the past fify years are comparable and---despite their severe consequences for public health--biochemically trivial. A few point mutations, the occasional gene duplication in malaria; but no new useful protein-protein interactions, no new molecular machines."

A good starting point might be with accurate quotations. Let's start there.

The Factician said...

A good starting point might be with accurate quotations. Let's start there.

Hmmm... Now who hasn't read the book? The complete quote from the book:

"HIV has killed millions of people, fended off the human immune system, and become resistant to whatever drug humanity could throw at it. Yet through all that, there have been no significant basic biochemical changes in the virus at all."

Indeed, he goes further (in an interview with World Magazine):

"Like malaria, HIV is a microbe that occurs in astronomical numbers. What's more, its mutation rate is 10,000 times greater than that of most other organisms. So in just the past few decades HIV has actually undergone more of certain kinds of mutations than all cells have endured since the beginning of the world. Yet all those mutations, while medically important, have changed the functioning virus very little. It still has the same number of genes that work in the same way. There is no new molecular machinery. If we see that Darwin's mechanism can only do so little even when given its best opportunities, we can decisively conclude that random mutation did not build the machinery of life."

Nice try to shift the goalposts, though...

Answer, please?

(And I might add, there are so many things wrong with that whole paragraph that it has me gasping at its inanity - and people pay Behe to teach their children - yowsers).

PaV said...

arthur hunt wrote:

Put another way, I always get the feeling when someone says as you do that they believe that breeders in the 50's and 60's in some way designed T-urf13 from first principles and then went in and deliberately manipulated the maize mt genome to place the T-urf13 gene there. This is, to be honest, patently ludicrous. Of course, maybe you have something else in mind. Feel free to elaborate.)

I hesitated to answer because I had no assurance you'd be able to respond, etc.

So, I'm glad we can continue here.

As to your query:

What I meant by artificial selection is not that "breeders" designed this protein in any way. I only meant to say that artificial selection does allow the continuation of a state of a species that nature itself might not allow. For example, if we threw a chihuahua to the wolves, literally, it would not survive. But, as 'man's best friend', he does. Similarly, the T-urf13 protein does, from what Wm. Dembski writes in "No Free Lunch", render maize male sterile and also makes it susceptible to a fungal toxin. So, if "nature" were to take its course, would we find the T-urf13 gene?

As to the CSI that this gene represents, I would refer you to NFL, pp. 218-219.

ERV said...

Sal-- I would hope Ms. Smith will articulate the details of what she believes Musgrave's phylogeny says and what the peer-reviewed papers say.

*blink*

Why? What are you going to offer me in return?


Hey PaV! Ill get to your Q's in a sec! Dinner time :) But as for the quote, thats on page 139, end of the upper right paragraph!

JanieBelle said...

Hehehe

That was fun to watch, ERV.

Hi Sal! I've missed ya', where ya' been?

(snicker)

Smokey said...

Sal,

You're being deliberately deceptive in pretending that Behe only made a claim about new genes, when he also made a much broader claim about new biochemical functions, conveniently quoted by PaV above.

In fact, HIV-1 is even more amazing in the number of different biochemical functions that evolution has packed into such a tiny protein.

Therefore, since you are being so deceptive (your violent metaphors give you away--do you have fantasies about beheading female scientists?), you still seem to have been lying when you claimed to want to continue the conversation. Moving the goalposts and demanding an answer to a misleading question is not conversation.

-----------
PaV,

I don't see any substantial difference between:

no significant basic biochemical changes in the virus at all.
and:
the evolutionary changes in both in the past fify years are comparable and---despite their severe consequences for public health--biochemically trivial. A few point mutations, the occasional gene duplication in malaria; but no new useful protein-protein interactions, no new molecular machines.

...but since your loony buds at UD have tried to claim that:

...single mutation of the kind required for malaria to become resistant to chloroquine–not the easiest mutation, to be sure, but still only a shift of two amino acids...

...means the same thing as two independent, sequential mutations, I'd be interested in your opinion.

Anonymous said...

erv--Why? What are you going to offer me in return?

So, you are just going to evade the question then?

PaV said...

the factician provides the quote:

"HIV has killed millions of people, fended off the human immune system, and become resistant to whatever drug humanity could throw at it. Yet through all that, there have been no significant basic biochemical changes in the virus at all."

(A page number would have helped. It's p. 139)

A fuller quote would begin this way:

"Although news stories righly emphasize the ability of HIV to quickly develop drug resistance, and although massive publicity makes HIV seem to the public to be an evolutionary powerhouse, on a functional biochemical level the virus has been a complete stick-in-the-mud. Over the years its DNA sequence has certainly changed. . . ."

Isn't it quite clear from that quote that Behe is talking about the "biochemical activity" of HIV-1, per se? IOW, the genetic machinery of HIV is still working much the same as 50 years ago---independently of what effects its having on its hosts. Your quote from "World Magazine" bears this interpretation out.

As I said over at UD: it's still HIV-1; i.e., it's not only a virus, but roughly the same kind of virus. What do we see that's novel in HIV-1 subtypes? Yes, the DNA sequences are different in the Vpu, and, yes, the different subtypes attack CD-4 in different ways, but what does any of that have to do with how the virus itself is operating as a biological entity? Note as well that Behe says: "Over the years its DNA sequence has certainly changed." But DNA sequence changes to the one side, what NEW biochemical functions have taken place in the virus itself? What's NEW and NOVEL about it? Very little. And this, after huge numbers of replications.

I still await ERV's response--although I suspect she's off somewhere studying.

[I'm having a terrible time reviewing and publishing posts. Any tips?]

art said...

Hi PaV,

You've got your own "private audience", as it were. Hope you have fun.

You said:"As to your query:

What I meant by artificial selection is not that "breeders" designed this protein in any way. I only meant to say that artificial selection does allow the continuation of a state of a species that nature itself might not allow. For example, if we threw a chihuahua to the wolves, literally, it would not survive. But, as 'man's best friend', he does. Similarly, the T-urf13 protein does, from what Wm. Dembski writes in "No Free Lunch", render maize male sterile and also makes it susceptible to a fungal toxin. So, if "nature" were to take its course, would we find the T-urf13 gene?

As to the CSI that this gene represents, I would refer you to NFL, pp. 218-219."


A few things. First, you may have missed it the first time I said it, but cms is something that occurs in nature. That's naturally, all by itself, without any help from humans. (It's one of many mechanisms by which plants "shift" their reproductive strategies over evolutionary times.) If someone on the anti-evolution side could explain to me the difference between a breeder choosing such a naturally-occurring trait, and its occurrence in the wild, I'd be quite pleased. (Keep in mind the context of this discussion - why is an occurrence in the wild of something once in 10^9 random trials a threat to Behe, but something in a cultivated field that also occurs once in 10^9 random trials is not. What is the difference? Why is 10^9 not always 10^9?)

Second, you are aware that "male sterile" is a crude way of saying "female", aren't you? I dearly hope you do not wish to imply, as Dembski does in NFL, that females are evolutionary dead-ends. (Abbie'll go medieval on you, I fear ... :-) ).

Third, I am afraid the CSI remark is being made to the wrong critic. Of course T-urf13 has no CSI. There is no such thing in nature. Direct experimental measurement (not the irrelevant arithmetic that we see in ID essays) shows us this in no uncertain terms.

The Factician said...

[I'm having a terrible time reviewing and publishing posts. Any tips?]

Not half the problems I'm having publishing posts at UD...

ERV said...

Pav-- Blogger hates everyone. It screws up links. It drops words randomly from your post. Its a crap shoot (so copy stuff before you hit 'PUBLISH').

What do we see that's novel in HIV-1 subtypes?
Thats a tricky question. As Ive said, we've barely scratched the surface of Subtype evolution... and then they fuse into Subtype AE or something stupid and were set back again.
But what would be 'different' enough to redeem Behe? Each Subtype has a gene called env that codes for the proteins on the outside of the virus. Now, HIV-1 Subtype B and C both have env... but they are folded in different ways. They use different co-receptors. Thats pretty dang biochemically significant.

But all retroviruses have env. And all their envs are radically different. Infecting different cells in different animals... Are they all the 'same' to Behe?

I dont know how you want me to answer?

As far as specifics about Vpu, yes, there are significant biochemical changes. Subtypes B and C have each picked up entirely novel binding motiffs, as well as the HUGE deal of creating a viroporin. And, we havent looked at all the subtypes yet.


Anon-- Ive answered that question multiple times. Someone even answered it for me in this comment thread by referring to what I already wrote. Your inability to read the English language is hardly my concern.

So fuck off. I have other things to do.

Unless you have something to offer me. In which case, I might think about copy/pasting my response again.

Smokey said...

PaV wrote:
"Isn't it quite clear from that quote that Behe is talking about the "biochemical activity" of HIV-1, per se?"

Yes, and Ms. Smith has described the new biochemical activities that have evolved.

"IOW, the genetic machinery of HIV is still working much the same as 50 years ago---independently of what effects its having on its hosts."

No, it isn't. That's why Behe is wrong.

"Your quote from "World Magazine" bears this interpretation out."

Yes, and Behe is wrong in every case.

"As I said over at UD: it's still HIV-1; i.e., it's not only a virus, but roughly the same kind of virus."

That's pathetic. Behe set the goalposts at new biochemical functions.

"What do we see that's novel in HIV-1 subtypes? Yes, the DNA sequences are different in the Vpu, and, yes, the different subtypes attack CD-4 in different ways, but what does any of that have to do with how the virus itself is operating as a biological entity?"

All the stuff that Ms. Smith describes above but you are ignoring. Behe is wrong. There's no way you can spin it outside of lying, PaV.

"Note as well that Behe says: "Over the years its DNA sequence has certainly changed.""

That just shows how pig-ignorant Behe is. The viral genome is RNA, not DNA. The DNA provirus is an intermediate.

"But DNA sequence changes to the one side, what NEW biochemical functions have taken place in the virus itself? What's NEW and NOVEL about it? Very little."

"Very little" is enough to show that Behe is dead wrong, because Behe claims that NOTHING is new and novel.

IOW, Behe is dishonest.

ERV said...

AAAAAAAAAAAAAAAAAAAAAAAAAAHAHAHAHAHAHAHAHAHA!

AAAAAAAAAAAAAAAAAAAAAAAHAHAHAHAHAHAHA!

THE LAUGHTER! THE PAIN! CANT LAUGH CANT STOP OMFG! AAAAAAAAAAAAAAHAHAHAHAHAHA!

I DIDNT NOTICE THAT SMOKEY! IN THE BILLIONS OF TIMES IVE GONE OVER THAT CHAPTER I DIDNT SEE THAT!!!

"Over the years its DNA sequence has certainly changed."

AAAAAAAAAAAAAAHAHAHAHAHAHAHAHA!

OOOOOOOOOW!

PaV said...

ERV:
"But what would be 'different' enough to redeem Behe? Each Subtype has a gene called env that codes for the proteins on the outside of the virus. Now, HIV-1 Subtype B and C both have env... but they are folded in different ways. They use different co-receptors. Thats pretty dang biochemically significant."

In describing the kinds of changes that happen in the malarial parasite, Behe very openly states that every possible change that could be made, has been made. He acknowledges that at one point or another every a.a. of the parasite genome could have theoretically been replaced given the huge number of replications. Being that he terms HIV-1 a "mutational powerhouse", this would apply a fortiori for HIV. That Vpu has had perhaps every single one of its a.a.'s replace at one time or another is a foregone solution. The binding between the Vpu protein and the various receptor sites, Golgi bodies, etc., given that only one or two a.a. substitutions may be needed to bring about a new binding capability, or a different folding pattern, would be almost expected.

What's being missed here is the point that Behe made in "World Magazine"; viz, that HIV-1 has perhaps "in just the past few decades . . . undergone more of certain kinds of mutations than all cells have endured since the beginning of the world."

Just think about that: HIV has mutated more than all cells from the beginning of life here on earth. And what do we find after all of those mutations? The HIV virus. It hasn't become something else. And, it's basic biochemistry hasn't changed. There are rearrangments of sequences, and these rearrangements have changed the affinities of its protein products, but it's still the same kind of organism. It's still HIV.

ERV:
As far as specifics about Vpu, yes, there are significant biochemical changes. Subtypes B and C have each picked up entirely novel binding motiffs, as well as the HUGE deal of creating a viroporin. And, we havent looked at all the subtypes yet.

Here's the link to an article that is looking at the similarity between Vpu and the M2 gene of Type A Influenza. The M2 produced protein of Type A Influenza, in mammalian cells, forms a viroporin. In the article I linked to, they demonstrate that Vpu "also forms
ion channels in planar lipid bilayers". It appears the basic chemistry of the Vpu, like the M2, spontaenously form such an 'ion channel'. It would be easy, I think, to simply suppose that somewhere along the line that SIV picked up the M2 from a chimp that was infected with Type A Influenza. The fact that the 'ion channel' seems to form spontaneously minimizes any supposed complexity that we want to attribute to Vpu on the basis of its forming a viroporin. Again, we might be dealing with just a few a.a. substitutions, and a "mutational powerhouse" like HIV should have no problem finding those a.a.'s.

There is something that deserves being pointed out---it's the obvious. In this attack on Behe's scholarship, we're comparing eukaryotes to viruses. They're completely different organisms. In fact, at Wikipedia you can find that viruses are not even considered to represent life. Now, we'll leave that argument alone, but the fact remains that viral biochemistry and genetics are not the same thing as for a eukaryote.

So, it seems to me that if we want to compare a CCC for a eukaryote to what happens in a virus, we're simply comparing apples and oranges. We need to recalculate.

Behe's CCC dervies itself from actual in vivo data. So he doesn't really calculate the probability in a strictly probabilistic fashion, as a statistician might, but just lets the numbers fall out of actual statistics. He relies on Nicholas White's calculations.

But, from a statistical point of view, if we said that the malarial parasite is 10^8 nucleotides long and we need two, simultaneous, point mutations to effect a change, then we would calculate 10^-8 x 10^-8= 10^-16. So, whence, 10^20? Well, it turns out that "in vivo" to get one point mutation in the malarial parasite ("in vitro" is different) we need 10^12 organisms; or, the odds are 1 in 10^12 for the first mutation, giving 10^-12 x 10^-8=10^-20.

But Behe tells us that HIV mutates 10,000 times faster than P.falciparum; and, it has a smaller genome. So, the equivalent of the CCC for HIV would be something like 10^-20 x 10^4 (for the first mutation) x 10^4 (for the second mutation) x 10^8/10^6(adjusting for genome sizes)= 10^8.

Well, isn't that what Musgrave calculated? But, as I pointed out earlier, this doesn't make Behe wrong about the CCC---it only makes his case stronger since, as Behe states, HIV-1 has perhaps "in just the past few decades . . . undergone more of certain kinds of mutations than all cells have endured since the beginning of the world."

And, it's still just HIV, even with all of those mutational possibilities given it.


arthur hunt:

(1) I was aware that cms happens in the plant genome, (2) I haven't any problems with females (pace ERV), (3) in terms random events, I would agree, there is no difference in terms of the "event" of T-urf13. (4) You say that CSI doesn't exist in nature: does that mean that you don't think there is such a thing as CSI at all, or, that if it exists, it exists outside of nature? (5) In "No Free Lunch", Dembski more or less concedes that the T-urf13 protein is CSI. He goes on to point out that T-urf13 is only 113 a.a. long, and that the probability of it being randomly produced falls below his Upper Probability Bound, meaning that we cannot infer design in its case. He also notes that not every position along the line of those 113 a.a.'s is critical, so that it falls even further below the UPB. T-urf13, in this sense, is certainly a curiosity, and can't easily be dismissed as either a trivial occurence or an example of design.

Since I don't have the time to become more expert in it than this, I'll just leave it at that: that T-urf13 is something that isn't easily dealt with from an ID perspective.

The Factician said...

Just think about that: HIV has mutated more than all cells from the beginning of life here on earth.

Yep, he sure did say that. Made me chuckle. That's a statement pulled straight out of his sphincter. The number of assumptions you would have to make to be able to calculate that number makes his statement totally full of poop.

PaV said...

Smokey:
" The DNA provirus is an intermediate."

Yes, Behe misspoke. (Unless he decided not to point out the distinction given the audience he was addressing. But, if so, it was the wrong decision.)

But it doesn't really change the argument; Behe thinks more in terms of a.a. changes anyway, and, whether it's DNA or RNA through reverse transcriptase that is coming up with the a.a. sequence, doesn't change the substance of the argument.

Smokey said...

PaV wrote:
"Behe's CCC dervies itself from actual in vivo data."

Now you're just lying. Behe's "CCC" is derived from a single quote-mine from a review.

Behe hasn't produced any data in a long, long, time, and I can predict with great confidence that his data drought will continue.

As for HIV, it's simple--Behe claimed that there were no significant biochemical changes in the virus at all. Blathering on about how it's still HIV-1 only highlights that you know that he's wrong.

Oh, and when you go back to UD, you might inform the moron who just posted there that evolutionary refinement for a virus means that it makes more viruses, not that it kills more people.

art said...

smokey, I think it's not appropriate to be calling PaV a liar. I suspect he believes the claims Behe has made about the source of Behe's "Edge of Evolution", and has probably never seen the context out of which Behe lifted his "derivation". This would make him (her?) mistaken, but not a liar.

For PaV's benefit, here is the part of the paragraph from White's review that Behe omits, the part that shows that White was not talking about two simultaneous mutations in a single protein when he tossed out the term 10^20. As always, enjoy:

“Chloroquine resistance in P. falciparum may be multigenic and is initially conferred by mutations in a gene encoding a transporter (PfCRT) (13). In the presence of PfCRT mutations, mutations in a second transporter (PfMDR1) modulate the level of resistance in vitro, but the role of PfMDR1 mutations in determining the therapeutic response following chloroquine treatment remains unclear (13). At least one other as-yet unidentified gene is thought to be involved. Resistance to chloroquine in P. falciparum has arisen spontaneously less than ten times in the past fifty years (14). This suggests that the per-parasite probability of developing resistance de novo is on the order of 1 in 10^20 parasite multiplications. “

PaV said...

art:
"For PaV's benefit, here is the part of the paragraph from White's review that Behe omits, the part that shows that White was not talking about two simultaneous mutations in a single protein when he tossed out the term 10^20."

If I gave the impression that I was talking about two simultaneous mutations in a single protein, then I'm sorry. In White's paper, I believe, he reviews the two common mutational sites, and I believe they involve two different proteins. But, again, it was basically two a.a. changes, though not on the same protein.

And, Smokey, why go on about "lying". If someone is on a blog and is lying, they're a real cad. It's one thing to disagree, to see things differently, and something far worse (and I think rare) for someone to just lie.

Torbjörn Larsson said...

Salvador Cordova

The first question I posed was, "did HIV-1 have Vpu when it entered humans?"

This is already answered in full in ERV's original post.

"“Sure it’s new in chimpanzees, but its not *new* in HIV-1!” Sorry, you’ll find no escape with that limp-wristed, ad hoc parry. SIVcpz Vpu and HIV-1 Vpu act in different ways, biochemically,"

So Behe claims no functional change in HIV, while ERV describes a lot of finds pertaining to before and after SIV evolved into HIV.

I know this as the last defense of the unable, to repeat an already answered question in varied forms. Pretending not getting an answer serves them as well when they want to claim that science has not the answer they don't want to hear.

I don't expect any new or *new* new questions. Yawn.

art said...

Hi PaV,

One last comment (probably for a while - I had a bit of free time this evening, but don't expect more long periods for posting flurries like this...) for the nite.

The excerpt from White's paper shows that White was not speaking about two mutations, but rather a combination of events that included the two events in the transporter as well as unspecified events in two other genes. That would mean a minimum of 4 mutational events, not two. This is the minimum number of events that may be properly linked with the value 10^20, if one is going to be citing White on this subject.

You mention a common claim, that "Just think about that: HIV has mutated more than all cells from the beginning of life here on earth." Have you ever thought about this statement? What does it mean? Bacteria, abundant eukaryotes, even humans have the property that 100% of their genomes are sampled by mutation in short spans of time (single generations, even). In my eye, 100% is 100%, you cannot get any larger. This is one way in which the claim you make is wrong.

It is also wrong when one considers the sheer numbers of possible pairwise (or higher order), epistatic combinations of changes that may be sampled. HIV is pretty limited, and no matter how many generations it goes thru, it won't even come close to the possibilities that are explored by larger genomes.

Bottom line - the assertion you make is intemperate, at the very least.

Torbjörn Larsson said...

PaV:

You say that CSI doesn't exist in nature: does that mean that you don't think there is such a thing as CSI at all, or, that if it exists, it exists outside of nature?

I can't answer for arthur hunt, but I can give you my view:

- Biology have had no need to use complexity measures to explain the characteristics of populations. Claiming that it is useful doesn't make it so.

- It is well known that there is no single measure of complexity that can capture all structures.

- And indeed, no one has presented a testable version of a general complexity measure for biology and gone on to find an application to creationist ideas, have they? "CSI" is currently an empty term, and I predict it will remain so.

Smokey said...

art wrote:
"smokey, I think it's not appropriate to be calling PaV a liar."

I didn't, Art. I said that he was lying. There's a big difference.

"I suspect he believes the claims Behe has made about the source of Behe's "Edge of Evolution", and has probably never seen the context out of which Behe lifted his "derivation"."

That doesn't mean he's not lying. He made a claim about the source without consulting the source. That is a false statement made with intent to deceive, aka a lie. "Liar" is ad hominem, and I don't do that.

"This would make him (her?) mistaken, but not a liar."

No, Art, believing the lies one tells doesn't mean that they are not lies, because evolutionary psychology tells us that humans are very prone to lying to themselves.

If PaV is merely mistaken, he'll retract and apologize for his false statement. What do you think he'll do?

Zachriel said...

PaV: "Just think about that: HIV has mutated more than all cells from the beginning of life here on earth. And what do we find after all of those mutations? The HIV virus. It hasn't become something else. And, it's basic biochemistry hasn't changed. There are rearrangments of sequences, and these rearrangements have changed the affinities of its protein products, but it's still the same kind of organism. It's still HIV."

Just think about it. Deuterostomes have mutated for hundreds of millions of years here on Earth. And what do we find after all those mutations? Deuterostomes. It hasn't become something else. And, it's basic biochemistry hasn't changed. There are rearrangments of sequences, and these rearrangements have changed the affinities of its protein products, but it's still the same kind of organism. It's still a Deuterostome with an anus at one end and a mouth at the other.

Some species can talk out of one end or the other.

Anonymous said...

The first question I posed was, "did HIV-1 have Vpu when it entered humans?"

A simple "yes", "no", or "I don't know" would suffice.


Many have pointed out that the answer has been provided many times, but the responders have assumed that Sal can comprehend basic english.

He can't.

Sal, the answer to your question is "no".

ERV said...

Anon-- ROFL! Please tell me youre joking?

Tyler DiPietro said...

"Just think about that: HIV has mutated more than all cells from the beginning of life here on earth. And what do we find after all of those mutations? The HIV virus. It hasn't become something else. And, it's basic biochemistry hasn't changed."

Define the "basic biochemistry" of something in a way that is meaningful beyond "I need a place to move these damn goalposts". Particularly, I would an actual explanation of why the subsequent evolution of HIV since entering humans is not significant that doesn't amount to pointing out the fact that it has been categorized under the same name.

Mike said...

Enought with the personal flames. Please discuss the science.

PaV said...

art:
"The excerpt from White's paper shows that White was not speaking about two mutations, but rather a combination of events that included the two events in the transporter as well as unspecified events in two other genes. That would mean a minimum of 4 mutational events, not two."

From what I remember of White's paper and Behe's discussion, there were 4 possible mutations at two possible sites; but only a minimum of one mutation at each site was needed.

art:

"It is also wrong when one considers the sheer numbers of possible pairwise (or higher order), epistatic combinations of changes that may be sampled."

But isn't that, in a sense, Behe's exact point: that nothing on earth has mutated as much as HIV? And, if something so simple as HIV (hardly qualifying itself as life) doesn't show any major novelty, then whence the novelty the fossil record assures us happened? Isn't that the basic argument?

IOW, HIV-1 doesn't appear to have the ability to lift itself up by its bootstraps. It contains, what, six genes, when it enters the human line, and after a mind-boggling number of mutations, it still has six genes. Doesn't this suggest some in-built limitation, one that is insuperable? If something so simple can't advance in complexity, why suppose more complex critters can?


art:
"HIV is pretty limited, and no matter how many generations it goes thru, it won't even come close to the possibilities that are explored by larger genomes."

I presume you mean in a recombinant way. Yes, larger genomes have many more possible recombinant configurations, but, the word is "re-combine", so that what is already present is simply re-arranged. Hence, as from the time of Bateson, the challenge to Darwinian theory has always been the rise of novelty. That gets us back to my previous comment: we don't see anything 'biochemically new' in HIV-1. The presence of subtypes and such simply highlights, it seems to me, that HIV-1 is capable of changing its sequencing, with the result that it affects the human hosts in new and novel ways, with some of these novelties having selective advantage; hence being preserved. But these are novelties that are exogenous, not endogenous. Behe is clear about concerning himself with endogenous changes. We just don't see it in HIV-1.

(N.B. Tyler, I hope this answers your request.)

zachriel:

"Some species can talk out of one end or the other."

And some species are capable of rational thought.

The Factician said...

But isn't that, in a sense, Behe's exact point: that nothing on earth has mutated as much as HIV?

That is exactly Behe's point. But it doesn't matter that Behe is trying to make that point. He has no data to back it up. He's pulling that point out of thin air.

How can you say that HIV has mutated more than all cells on earth when we know neither:

a) how many changes HIV has possibly made since it first infected humans

b) how many mutations all the cells on earth have undergone since the beginning of life on earth

He has neither numerator, nor denominator, and yet he tries to make that assertion. It's completely bogus...

Anonymous said...

Pav,

I am no expert on this, but I think that your explanation is more confusing. The diagram from an earlier post is quite clear. Vpu seems to be doing novel functions that were not present in earlier forms of the virus.

You wording also implies that more genes='better' virus. Given the selection pressure that virus is under from our immune systems, I would expect that HIV would have a 'streamlined' genome i.e. a genome that is replicated faster. Viruses with 'extra' genes may have just been selected out.

On that note, I think you have to be cautious when using words like 'complexity' with respect to biological organisms/systems. The fact that the virus has gained new functions whilst retaining the same number of genes is quite nanotechnologcial feat. Certainly, a lot more impressive than just getting a new gene(s). Perhaps you could share your definition of 'complexity' with the rest of us.


Cheers

ernestog said...

Sorry, last comment was from me.

Smokey said...

PaV wrote:
"From what I remember of White's paper and Behe's discussion, there were 4 possible mutations at two possible sites; but only a minimum of one mutation at each site was needed."

You're wrong. Nothing in White's paper or the primary literature (that stuff with the real data) indicates that. Moreover, Behe explicitly described a "single mutation" that changed two amino acids, so attributing this to Behe is false.

Everybody notice how, in this case, PaV is employing rank dishonesty in trying to conflate Behe's false assertions with White's review paper?

"But isn't that, in a sense, Behe's exact point: that nothing on earth has mutated as much as HIV?"

Behe has no idea whether that is true or not. Nor do you.

"And, if something so simple as HIV (hardly qualifying itself as life) doesn't show any major novelty, ..."

But it does show multiple major novelties, so Behe is wrong.

"...then whence the novelty the fossil record assures us happened? Isn't that the basic argument?"

Science doesn't operate by "arguments," it operates using hypotheses, predictions, and data. Your hero, Behe, lies and presents hypotheses as data, and has so little faith in any of his hypotheses that despite having his own lab and money, has not presented a single datum from a test of his hypothesis.

Behe is a fraud.

"IOW, HIV-1 doesn't appear to have the ability to lift itself up by its bootstraps."

It's a parasite, so your metaphor is irrelevant.

"It contains, what, six genes, when it enters the human line, and after a mind-boggling number of mutations, it still has six genes."

Counting genes in a genome that it highly length-constrained is a deliberate deception, if one is trying to assess complexity.

How many different transcripts are made from the HIV-1 genome? How many polypeptides are translated from those polycistronic transcripts? That shows the complexity, not a silly counting of genes.

"Doesn't this suggest some in-built limitation, one that is insuperable?"

Yeah. Packaging of the RNA (not DNA as Behe falsely claimed) genome into the virion is the limitation, moron. That's why the number of different polypeptides and biochemical functions is so amazing.

"If something so simple can't advance in complexity, why suppose more complex critters can?"

If you think it's so simple, why aren't you dedicating your life to ridding the world of the enormous suffering caused by this virus?

"I presume you mean in a recombinant way. Yes, larger genomes have many more possible recombinant configurations, but, the word is "re-combine", so that what is already present is simply re-arranged."

No. In biology, we have names for different types of recombination-homologous and nonhomologous. You are describing only the former, while the latter generates much more novelty. This, of course, is why you dishonestly pretend that it doesn't even exist.

"That gets us back to my previous comment: we don't see anything 'biochemically new' in HIV-1."

But as Ms. Smith has repeatedly shown, that claim is a bald-faced LIE.

"The presence of subtypes and such simply highlights, it seems to me, that HIV-1 is capable of changing its sequencing,..."

This just shows your ignorance of the most basic biology. "Sequencing," used in the active sense, is ONLY used to refer to what we humans do to DNA.

"We just don't see it in HIV-1."

We do; your eyes are simply closed. If you think that HIV is so simple, why are you arguing on a blog instead of getting a grant from the DI to cure AIDS?

Your arrogance, particularly in the context of your aggressive ignorance and dishonesty, is amazing. The fact that you won't lift a finger to test an ID hypothesis or solve the problems caused by an allegedly simple virus shows that you know full well that you are lying, PaV.

Zachriel said...

zachriel: Some species can talk out of one end or the other.

PaV: "And some species are capable of rational thought.

Quite so! But (assuming you are speaking of humans rather than some intelligent species of cephalopod), they are still Deuterostomes!

PaV: "if something so simple as HIV (hardly qualifying itself as life) doesn't show any major novelty, then whence the novelty the fossil record assures us happened? Isn't that the basic argument?

Yes, that is the basic fallacy.

Your first problem is with your use of the term "major". Sure, human's have undergone some minor changes, but they're still Deuterostomes; tubes with with various attachments for shoving food in one end. Rather disgusting habit, eating other organisms, but that's what Deuterostomes do.

But the bigger problem is the invocation of the strawman argument. The Theory of Evolution doesn't predict that organisms will evolve to become more complex, or tend to grow big noses. Try and think about what the Theory of Evolution actually predicts.

We can directly observe rates of morphological evolution. And this rate of change is much, much more rapid than required to explain "the novelty the fossil record assures us happened."

The Factician said...

But isn't that, in a sense, Behe's exact point: that nothing on earth has mutated as much as HIV?

Ok, so I can't let this go. I had to find a tiny bit of data to point out the ridiculousness of this argument.

When a person is about to die of AIDS, they have the highest concentration of HIV in their blood that they will ever have. Rougly 1e6 (1e6=10 to the power of 6) phages per mL of blood. They have about 5000 mL of blood. That means they have roughly 5e9 HIV particles in their body. Roughly.

If every human on earth were in end stage AIDS disease (all 6 billion of us), there would be 3e19 HIV particles in the whole wide world. We know there is something less than this number, but work with me.

In the ocean, there are 1.3e23 mL of water (I'm using mL to keep the units simple). There are roughly 1e9 bacteriophage (viruses that kill bacteria) per mL of ocean water, meaning there are 1.3e32 phages in the ocean.

So, if every human on earth were infected with end-stage HIV (which we are not) there would still be 10000000000000X as many bacteriphage in the ocean as there are HIV in humans. And that's just the bacteriophages.

Kinda makes you wonder why anyone listens to Michael Behe when he's so full of shit.

Mike Dunn said...

This is a riot. You guys are wasting all this time, shadow-boxing with an obscure, ignorant grad student (Smith) over a trivial microbe, HIV.

It has a trivial amount of base-pairs (9100) and, on its best day, 8 genes.

More importantly, it has such low titer in AIDS patients, that it is practically non-detectable.

Have none of you read the journal Cancer Research, which debunked this pussy-cat virus 20 years ago?!!?

So-called "human" retroviruses simply have no clinical relevance, let alone evolutionary relevance.

If AIDS viruses were pathogenic by killing susceptible lymphocytes, one would expect AIDS to correlate with high levels of virus infiltration and expression, because uninfected cells would not be killed by viruses nor would unexpressed or latent viruses kill cells. As yet no report on virus titers of AIDS patients has appeared, despite the record interest in the epidemiology and nucleic acid structure of this virus (13, 27, 223). In view of the consistent antiviral immunity of AIDS patients and the difficulties in isolating virus from them (213), the virus titers are probably low. Titers have been said to range between only 0 and 102 per ml blood (213).8
Proviral DNA has been detected in only 15% (9 of 65) AIDS patients; in the remaining 85% the concentration of provirus, if present, was apparently too low for biochemical detection (246). Moreover, among positive samples less than 1 in 102 to 103 lymphocytes contained the provirus (246). Viral RNA was detected in 50 to 80% of AIDS blood samples. However, among the positive samples, RNA was found in only less than 1 of 104 to 105 presumably susceptible lymphocytes (247). The relatively high ratios of provirus-positive (10-2 to 10-3) to viral RNA positive cells (10-4 to 10-5) of AIDS patients indicate latent infections. Further there is no evidence that the virus titer or the level of virus infiltration increases during the acute phase of the disease. It is probably for this reason that cells from AIDS patients must be propagated several weeks in culture, apart from the host's immune system, before either spontaneous (210-214) or chemically induced (248) virus expression may occur. Further, the AIDS virus is completely absent from the Kaposi sarcoma (27, 246), which is associated with 15% (216) to 30% (249) of AIDS cases and is one of the most characteristic symptoms of the disease.
Similar extremely low levels of virus infiltration and expression were also recorded in AIDS virus-associated brain disease (274). Likewise, in interstitial lymphoid pneumonia less that 0.1% of lung cells expressed viral RNA (275).
Indeed there is evidence that even latent virus may not be necessary for AIDS, since 85% of AIDS patients lack proviral DNA (246) and since over 10% of AIDS patients have been observed to lack antiviral immunity (214, 221, 222, 234). Further, in a study from Germany 3 of 91 AIDS patients were found to be virus free, based on repeated negative efforts to detect antibody or to rescue virus.9
It is concluded then that the AIDS virus infects less than 1%, and is expressed in less than 0.01%, of susceptible cells both in carriers with or without AIDS. This raises the question of how the virus could possibly be pathogenic and responsible for immunodeficiency or other diseases. For instance even if the virus were to claim its 10-4 or 10-5 share of T-cells that express viral RNA every 24 to 48 h, the known eclipse period of retroviruses, it would hardly ever match or beat the natural rate of T-cell regeneration (176).
All other viruses function as direct pathogens only if they are biochemically active and expressed at high levels. For instance, the titers that correlate with direct pathogenicity for avian retroviruses are 105-12 (31, 35, 250)4 and they are 104-7 for murine retroviruses (12, 38, 40, 42, 251) (Section B). Hepatitis viruses reach titers of 1012-13 when they cause hepatitis (15), and latent infections are not pathogenic (83). Further, the very low levels of AIDS virus expression in vivo are difficult to reconcile with reports based on in vitro studies with synthetic indicator genes that the AIDS virus encodes a potent transcription-stimulating protein (28, 153, 245). Clearly such activators are not at work in vivo.
The extremely low virus titers of symptomatic and asymptomatic carriers also explain why infection by the virus in the United States is essentially limited to contacts that involve transmission of cells (244) rather than being transmitted as a cell-free, infectious agent like pathogenic viruses. For instance, among 1750 health care workers with exposure to AIDS, only 1 or 2 were found to be antibody positive (252). Another study failed to find a single antibody-positive person among 101 family contacts of 39 AIDS patients, all of whom had lived in the same household with an AIDS patient for at least 3 months (253).

The Factician said...

^^^

And so the fun begins! Weeeeee!

Hermagoras said...

There must a Duesberg analogy to Godwin's law:

As a defense of pseudoscience grows more desperate, the probability of Peter Duesberg being portrayed as a hero/rebel/pioneer approaches one.

Anyway, refutations of his crap are not hard to find.

Mike Dunn said...

I love it -- Hermagoras, an English Professor is critiquing the peer-reviewed work of biochemist, member of the National Academy on an issue of biochemistry!

And, he/she is arrogant to boot!

Stick to Shakespeare, Dork.

Hermagoras said...

Mike,

Hermagoras, an English Professor is critiquing the peer-reviewed work of biochemist, member of the National Academy on an issue of biochemistry!

Not at all: I'm merely pointing to the critiques of scientists. Thousands of peer-reviewed papers get published annually. One way people like me can assess them is to see how they've been treated. Has Duesberg been ignored? No. Has he been rejected? Yup. Almost all the 56 citations of that article in Google scholar that are not by Duesberg are identifiable as refutations of Duesberg.

I'm not scientifically trained enough to do the critiquing myself; I'm just pointing to the scientific consensus. Duesberg is widely held to be a crank on this issue within the scientific community.

I also mentioned that HIV denialists/ Duesberg defenders pop up routinely in pseudoscience discussions. Your appearance here is almost predictable.

H

Mike Dunn said...

Hermagoras,

Instead of wasting time with your utter lack of any knowledge or expertise on the issue, why not address the central claim made by Dr. Duesberg in the peer-reviewed paper I cited: Namely,

There is an absence of HIV in many AIDS patients.

Proviral DNA has been detected in only 15% (9 of 65) AIDS patients; in the remaining 85% the concentration of provirus, if present, was apparently too low for biochemical detection (246).

246. Shaw et al. Molecular characterization of human T-cell leukemia (lymphotropic) virus type III in the acquired immune deficiency syndrome. Science, 226:1165-1167, 1984.

If you can't find pro-viral DNA of HIV in AIDS patients without using PCR, really, how much cellular damage can said virus be causing?

Get a clue.

The Factician said...

^^^^

Looks like erv wore her "crazy-magnet" earrings to work today...

MIke Dunn said...

Again, this is a riot!

I cite 2 papers in prestigious peer-reviewed journals: Cancer Research and Science.

In response -- from the so-called "Evidence Based Crowd" -- I get:

1. 2 obnoxious sock-puppets, including an English Professor and some jerk, named "The Factician"

2. Neither of whom address the point made in said scientific papers.

Namely, in many AIDS patients, pro-viral DNA of the dreaded virus cannot be detected.

Ain't that a problem?

No wonder why Neo-Darwinists or whatever they call themselves are getting battered by ID. They are mostly incompetent, junior-varsity, sock-puppets, still living with and/or sucking off their parents, at best, doing some meaningless science about which no sane person in the real world gives a hoot.

Keep blogging, Amateurs! You're really making important progress. LOL!

Kristjan Wager said...

mike, do you actually have an argument or any data in there? Or are you just babbling?

I like the fact that (the oft-debunked) Duesberg is getting invoked, when Behe bases his premise on the existence of HIV/AIDS. Some neo-Creationists are also AIDS deniers, but Behe isn't one of them to my knowledge.

Mike Dunn said...

For Christ's sake, a third bozo now appears? At least Kristjan Wager has a name.

You ask:

do you actually have an argument or any data in there?

Data: Proviral DNA has been detected in only 15% (9 of 65) AIDS patients; in the remaining 85% the concentration of provirus, if present, was apparently too low for biochemical detection .

Source: Shaw et al. Molecular characterization of human T-cell leukemia (lymphotropic) virus type III in the acquired immune deficiency syndrome. Science, 226:1165-1167, 1984.

Argument: In these 56 AIDS patients, pro-viral DNA of HIV was not detected in white blood cells. Therefore, HIV was not present in sufficient titer to cause any cell damage.

Do you folks read? I spelled this out before.

This is the best of Darwinian bloggers?!!?

The Factician said...

Yup, didn't detect proviral DNA in 1969 either. Summer of love.

Go figure...

ERV said...

Factician-- I am the Kwisatz Haderach of woo.

Mike, hon, youre on the wrong thread. I know, its easy to get Creationism/Denialism threads mixed up, but this is the post youre looking for.

Smokey said...

Mike Dunn said...
"I love it -- Hermagoras, an English Professor is critiquing the peer-reviewed work of biochemist,..."

Um, no, Mike, that paper is:

a) not what scientists call "work" (it's opinion, not data), and
b) it probably wasn't peer-reviewed at all. Reviews rarely are.

"...member of the National Academy on an issue of biochemistry!"

It isn't an issue of virology?

"...why not address the central claim made by Dr. Duesberg in the peer-reviewed paper I cited:"

Why not support your claim that the paper was peer-reviewed, Mike. It's opinion, not primary literature.

"There is an absence of HIV in many AIDS patients."

Now you're just lying. An inability to detect something in a single trial is not a convincing argument for its absence.

"Proviral DNA has been detected in only 15% (9 of 65) AIDS patients;..."

Now, why did you fudge a lack of detection as nonexistence?

"If you can't find pro-viral DNA of HIV in AIDS patients without using PCR, really, how much cellular damage can said virus be causing?"

You're probably looking in the wrong cells, dork.

"I cite 2 papers in prestigious peer-reviewed journals: Cancer Research and Science."

There's no evidence that the first paper was peer-reviewed, and you misrepresented the second.

"Argument: In these 56 AIDS patients, pro-viral DNA of HIV was not detected in white blood cells. Therefore, HIV was not present in sufficient titer to cause any cell damage."

Therefore, either there was a technical limitation in detection or the virus was in cells other than white blood cells.

Next time, try citing a paper from Duesberg that has some actual work (new data) in it. Just like Behe, Duesberg has so little confidence in his position that he has always been afraid to put it to the test.

Mike Dunn said...

Ahh, the 4th person - named by his beloved parents at birth, "Smokey":)

I guess it's kinda like "attack of the clones."

What an ignorant liar you are, Smokey.

not what scientists call "work" (it's opinion, not data), and
b) it probably wasn't peer-reviewed at all. Reviews rarely are.


Cancer Research is a prestigious journal in the scientific literature, doofus.

Here's its policy:

Cancer Research publishes significant, original studies in all areas of basic, clinical, translational, epidemiological, and prevention research devoted to the study of cancer and cancer-related biomedical sciences. Scientific topics include: cell and tumor biology; clinical research; endocrinology; epidemiology; experimental therapeutics, molecular targets and chemical biology; immunology; molecular biology, pathobiology and genetics; prevention. Thus its publication scope covers all subfields of cancer research. Papers are stringently reviewed and only those that report results of novel, timely, and significant research and meet high standards of scientific merit will be accepted for publication.

You think "Review" papers somehow don't count?!!? You really must be a scientific grinder of the highest order.

You would kill to publish even a letter in a journal as prestigious as Cancer Research.

Navigating your utter tripe, here's your answer:

Therefore, either there was a technical limitation in detection or the virus was in cells other than white blood cells.

Or the virus wasn't there, Dork -- and there's a hole in the evidence.

Tyler DiPietro said...

"Cancer Research is a prestigious journal in the scientific literature, doofus...You think "Review" papers somehow don't count?!!?"

It is truly amusing that you can't see the flaw in this. Hint: A "review" isn't the same thing as a "research paper".

The Factician said...

You would kill to publish even a letter in a journal as prestigious as Cancer Research.

I killed a man once to get a letter in Cancer Research.

Oh, the crazy days of my youth!

*whistles*

PaV said...

The Factician:

"So, if every human on earth were infected with end-stage HIV (which we are not) there would still be 10000000000000X as many bacteriphage in the ocean as there are HIV in humans. And that's just the bacteriophages."

Well, viruses aren't cells, and Behe was talking about cells. That said, I don't have access to the "World Magazine" article, and hence don't know for sure what he had in mind. (Was he talking about eukaryotic cells only?).

Anyway, because of its high replication rate, high mutation rate, and high rate of mutations due to reverse transcription, HIV is certainly well-sampled evolutionarily.

zachriel:

Are "deuterostomes" a species?

smokey:

"You're wrong. Nothing in White's paper or the primary literature (that stuff with the real data) indicates that. Moreover, Behe explicitly described a "single mutation" that changed two amino acids, so attributing this to Behe is false."

I've read EoE somewhat closely. I read White's review somewhat closely. White's paper was rather thoroughly discussed at UD. I believe you're wrong in both instances you cite. But notice, I'm not accussing you of "lying".

"Behe has no idea whether that is true or not. Nor do you."

If you think some species has mutated more, I'm sure that Behe would appreciate you pointing it out to him.

"Science doesn't operate by "arguments," it operates using hypotheses, predictions, and data."

Darwin said of his Origin of Species that it was a long, extended argument. So, I guess the Origin of Species ought to be ignored as well. Apparently it doesn't qualify as science either.

"How many different transcripts are made from the HIV-1 genome? How many polypeptides are translated from those polycistronic transcripts? That shows the complexity, not a silly counting of genes."

It seems to me that you've described its variability, not its complexity. I wasn't trying to insult the poor little HIV when I said that is was simple. I was making the point that adding complexity to something so simple should be more easily digested than something that is constructed in a more complex fashion. As an analogy: if you're a juggler, going from 3 to 4 balls is a lot easier than going from 7 to 8.

"No. In biology, we have names for different types of recombination-homologous and nonhomologous. You are describing only the former, while the latter generates much more novelty. This, of course, is why you dishonestly pretend that it doesn't even exist."

Yes, I must be dishonest. Now, since non-homologous recominations generates much more novelty, where, exactly, in the HIV do we see this novelty? Please don't confuse HIV as an entity, with what it does to some other entity.

"Yeah. Packaging of the RNA (not DNA as Behe falsely claimed) genome into the virion is the limitation, moron. That's why the number of different polypeptides and biochemical functions is so amazing."

It's simply marvelous, smokey, that you find what HIV does to be amazing. However, I'm not so impressed. Darwinist claim that if you can get something to replicate and to mutate, then the sky (literally) is the limit. Here we have something that replicates faster than almost anything we know, something that mutates more than anything we know, and it still hasn't made it to the level of "life". It can't even make it to the starting line. Isn't that interesting?

I guess you mean to say that this poor, old HIV CAN'T evolve a larger envelope to store more nucleotides. Well, if it can't do that--given that it already has a gene for the envelope, than how in the world is it going to evolve a new gene? You keep accussing me (and I bet everyone you disagree with) of lying. Well, are you lying to yourself about what RM+NS can really do. I think you are.

"But as Ms. Smith has repeatedly shown, that claim is a bald-faced LIE."

No, smokey, this is the issue that is being discussed, despite your intemperate remarks to the contrary.


"Your arrogance, particularly in the context of your aggressive ignorance and dishonesty, is amazing."

The degree to which you project onto others is really a marvel to behold.

PaV said...

art:

"HIV is pretty limited, and no matter how many generations it goes thru, it won't even come close to the possibilities that are explored by larger genomes."

Art, yes, the more complexity that is present, and the more kinds of combinations that can be explored amongst this complexity, then the greater the possibility for a higher level of complexity to appear, but how does this obviate the objection that the initial level of complexity must first be explained.

They have all kinds of LEGO sets, including all kinds of interesting pieces. Kids, my nephew especially, can build all manner of designs exhibiting all manner of complexity. And, it's possible for my nephew to interchange portions of something he's already built to come up with something even more complex and interesting. But, we're always left with the question: where did these parts come from? In the case of what my nephew does with the components, easily, this is called "intelligent design". And, if we were to go to the factory where these LEGO blocks and stuff are produced, we'd run into more "intelligent design". It seems to me all of this is self-evident. But, of course, I suspect you might disagree with me.

Thank you, BTW, for your very engaging and gentlemanly style of discourse. I only wish I found more of it in the "blogosphere".

olegt said...

pav,

It seems to me that most of your problems stem from a simple misunderstanding: evolution isn't supposed to proceed from simple to complex. It proceeds to a locally best position. Whether it leads to a simpler or more complex organism does not matter.

Once you realize that, you can drop the tiresome question why is a virus still a virus?

The Factician said...

Well, viruses aren't cells, and Behe was talking about cells.

Well, he talked about HIV in the sense that HIV had mutated more than anything out there. Wasn't that the quote? And yet I demonstrated that HIV is only a very small part of the viral biosphere, much less the cellular biosphere. But let's not let Behe being wrong stop us...

Anyway, because of its high replication rate, high mutation rate, and high rate of mutations due to reverse transcription, HIV is certainly well-sampled evolutionarily.

Well-sampled? That's a rather vague statement, but I think I could agree with you on that. Completely sampled? Not even close. HIV over decades in humans hasn't come close to sampling the amount of variation that all the phages in the ocean will sample tomorrow.

And the next day.

And the next day.

Now what about over the next, oh, say million years? Or billion?

Do you see how far off Dr. Behe is? How terribly far off he is from being able to suggest that HIV is even close to being saturated for mutation? Though he may think that it's "gosh darn mutated alot" that's a long shot from sampling all the possible mutations and mutant varieties out there.

But again, let's not let Behe being wrong stop us...

PaV said...

the factician:

"Do you see how far off Dr. Behe is? How terribly far off he is from being able to suggest that HIV is even close to being saturated for mutation?"

I finally got a look at "World Magazine". It's a Christian magazine, not a scholarly one. What Behe said, he said in an off-hand manner. He also was speaking about some unstated, specific type of mutation. I'll guess that it's recombination; but that's simply a guess. Neither you nor I know for sure. If he means any old kind of mutation that has happened in cells since the beginning of the world, well I can make an argument up to about 10^25 or 26th. But, of course, there likely is that many bacteria right now. So, let's assume he meant, as he said, "more of certain kinds of mutations" than "every" mutation that has ever occurred. You can always email him to find out.

The Factician said...

Pav,

Oy. I give up. You win. HIV has had more mutations than ever possible in the history of the earth, and still hasn't changed into a cabbage. Even though there's a relatively small number of HIVs in the world. Even though Behe is wrong.

Where do I get my UD badge and learn the secret handshake?

*goes to mix a martini*

PaV said...

olegt:

"It seems to me that most of your problems stem from a simple misunderstanding: evolution isn't supposed to proceed from simple to complex. It proceeds to a locally best position."

I'm not experiencing any problems that I know of. Today, in fact, I had a physical, and my LDL is the best my doctor has ever seen. :)

But, more seriously, let me just ask you this: has HIV, after this veritable "mutational powerhouse" has replicated an astronomical number of times, "proceed[ed] to a locally best position"?

In terms of its genome, and internal functioning, not much has changed. If we consider the various groups and subtypes, well, then, yes, maybe we can call these "locally best positions"; but, as I stated elsewhere, here is this fabulous replicator, fabulous mutator, and yet it really hasn't moved much has it? Can we isolate any kind of "intermediate form"? No. It's a virus. All the subtypes are viruses. Am I missing something?

The Factician said...

But, more seriously, let me just ask you this: has HIV, after this veritable "mutational powerhouse" has replicated an astronomical number of times, "proceed[ed] to a locally best position"?

Yes.

In terms of its genome, and internal functioning, not much has changed. If we consider the various groups and subtypes, well, then, yes, maybe we can call these "locally best positions"

I'm glad we agree on at least one point.


but

It's always the "but", isn't it?

As I stated elsewhere, here is this fabulous replicator, fabulous mutator, and yet it really hasn't moved much has it?

I mean, aside from the rather large biochemical changes that erv documented, you're right, it hasn't moved much. Or rather, aside from the places where it moved a bunch, it hasn't moved much.

Can we isolate any kind of "intermediate form"?

Now that we're trying, yes. I guarantee the forms that are isolated in 2050 will look somewhat different from the forms now. Indeed, I'll bet an epidemiologist (or erv even!) could tell you how some of the subtypes in 2007 look different from subtypes circa 1987.

No. It's a virus. All the subtypes are viruses.

You're right. It's still not a cabbage. Wait, who thinks it should be a cabbage?

Am I missing something?

Yes. Yes, you are.

ERV said...

PaV-- Ill try to get you a more thorough response soon, but I will be driving 7 hours either Saturday or Monday, and I still have two tests to deal with, and I NEED to do laundry, and I have to work all day Monday (maybe in addition to the 7 hour drive)... Jesus Im going to bed after this post...

LOL Anyway, short answer-- Bigger /= better for retroviruses. There is a reason retroviruses are ~10 kilobasepairs long or smaller (they cant keep getting bigger and bigger for a multitude of biochemical reasons).

Also, look at the HIV genome: Link!

All of those genes? All of those overlapping genes and broken up genes, and some of those genes get cut up into several proteins, and some of those proteins have several domains... And HIV-1 has one promoter.

One.

The transcription and translation of each of those proteins is an intricate dance-- adding in a Vpu or Vpx is a BIG deal. Adding new protein binding sites, adding new protein domains, thats a BIG deal. You cant just 'add' stuff to HIV and expect the virus to work.

It wont.

We've tried.

But evolution did it.

Its not *just a virus*.

PaV said...

Factician:

Go have another martini! :)

olegt said...

pav said:But, more seriously, let me just ask you this: has HIV, after this veritable "mutational powerhouse" has replicated an astronomical number of times, "proceed[ed] to a locally best position"?

OK, now we're going somewhere. You've got the random part. Let me reinforce it by using a simple example and then we'll move on to the next stage. In the process I will sneak some non-random part, which plays an important role.

Picture mutations as a random walk. Note, however, that the surface is not flat: it goes up if the mutation is harmful and down if the mutation confers an advantage. Some mutations make no difference, which means the surface is level in that direction. So, the random motion proceeds through a landscape.

Since "bad" mutations lead to a decreased fitness, we can say that directions leading up are not explored (because explorers become less numerous and die out). To the contrary, better fit organisms multiply faster, so the most explored directions are those leading downwards. To simplify the picture further, we can say that all random steps are attempted, but those which lead up are rejected.

Now we see that the random walk is no longer completely random: it is biased towards lower altitudes. It will gradually proceed downward until it descends all the way into a valley (a local minimum). And there it will be stuck! No matter how long the random walker explores the valley, it has nowhere to go: all directions lead up. Even if there is a deeper valley nearby, it needs to climb over a pass in order to get there, and this may be difficult.

Let me recap. Mutations alone are like a purely random walk: they don't make an organism better in any sense. We need a landscape to select "better" organisms. "Better" means more fit in this particular landscape. Something is missing, however: the landscape picture led us into an apparent evolutionary blind alley: the biased random walk has found a local minimum and got stuck in it foreva.

But have no fear, it'll manage to get out!

olegt said...

Our previous simplified model (a random walk biased by a landscape) got to a local minimum and is stuck. No matter how many mutations happen, no further improvements are possible, so it'll be the best possible position locally, but of course not globally. It could have done better if it climbed over a pass, but our rules do not allow that.

Can we improve this model? Sure. Landscapes are not static. For instance, the climate can change. Furthermore, for viruses the environment is living organisms, which themselves can change. Lastly, a virus can also get into a new host. So the landscape is dynamic.

So now the landscape has changed (think of an earthquake). The old valley, in which the random walk was hopelessly stuck, gets connected to a deeper valley. The random walk goes further down and finds a new local minimum where it gets stuck until the next earthquake.

So, to make a connection with out viruses, a fast mutation rate alone only guarantees that the virus will quickly find its locally best position. It can then remain stable for ages, until the environment changes again.

I am totally clueless in virology, but I would venture a guess that when SIV jumped from monkeys to humans, it was given precisely this new opportunity to improve itself in a new environment. Which it did rather quickly, on the scale of a few decades---thanks to the large mutation rate! It was mutating fast in the previous host, but there presumably it has already adapted pretty well, so any further "improvements" were slow.

To conclude, random mutations are not enough, you need a landscape to make improvements through natural selection. The mutation rate alone only determines how fast a virus adapts to a given environment (very quickly). Further changes occur when the environment changes (dynamic landscape).

Smokey said...

Mike Dunn wrote:
"Cancer Research is a prestigious journal in the scientific literature, doofus."

It's second-tier at best.

"You think "Review" papers somehow don't count?!!?"

Think? Hell, I know that's not talking about reviews, because they don't contain novel data. No review I've written has been peer reviewed. What about your reviews, Mike?

"You would kill to publish even a letter in a journal as prestigious as Cancer Research."

Let's see if you're willing to put your money where your mouth is. I'll bet you $10,000 that I've published multiple papers in journals far more prestigious (i.e., higher impact factors) than Cancer Research. I predict that you don't really believe what you wrote, and you won't have the guts to take my bet. We'll send cashier's checks to Abbie, and I'll point you to my identity and my publication record.

Smokey said...

PaV bloviated:
"I've read EoE somewhat closely."

Apparently not.

"I read White's review somewhat closely. White's paper was rather thoroughly discussed at UD."

The idea of thoroughly discussing a REVIEW is simply idiotic, PaV. Real scientists discuss the actual data published in the primary literature, not reviews.

"I believe you're wrong in both instances you cite. But notice, I'm not accussing you of "lying"."

Of course not, because I'm correct:

“The likelihood that Homo sapiens achieved any single mutation of the kind required for malaria to become resistant to chloroquine–not the easiest mutation, to be sure, but still only a shift of two amino acids..."

"If you think some species has mutated more, I'm sure that Behe would appreciate you pointing it out to him."

No, he wouldn't, just as he is too cowardly to respond to Abbie's shredding of his lies about HIV.

"Darwin said of his Origin of Species that it was a long, extended argument. So, I guess the Origin of Species ought to be ignored as well. Apparently it doesn't qualify as science either."

Nope. It contained all three--hypotheses, predictions, and data. My point is that you and Behe lack the guts/faith to do any actual science and test any predictions to produce new data. You are intellectual cowards who produce rhetoric instead of new knowledge about the world.

"It seems to me that you've described its variability, not its complexity."

It is clear to me that you don't know shit about HIV.

"Yes, I must be dishonest."

You clearly are.

"Now, since non-homologous recominations generates much more novelty, where, exactly, in the HIV do we see this novelty?"

Viral transduction, obviously. HIV is much more than the minimal gag-pol-env retroviral genome.

"Please don't confuse HIV as an entity, with what it does to some other entity."

I'm not the confused one.

"It's simply marvelous, smokey, that you find what HIV does to be amazing. However, I'm not so impressed."

Then find a vaccine for it.

"Darwinist claim..."

Which darwinist?

"... that if you can get something to replicate and to mutate, then the sky (literally) is the limit."

Literally? No, you're simply lying. No one has ever said that literally, Darwinist or not. Do you even know what "literally" means?

"Here we have something that replicates faster than almost anything we know,...."

You're lying again. I can point you to literally thousands of viruses that replicate more quickly than HIV. BTW, "fast" is an adjective, not an adverb.

"... something that mutates more than anything we know,"

You're lying yet again. RNA viruses mutate much more than retroviruses.

"... and it still hasn't made it to the level of "life". It can't even make it to the starting line. Isn't that interesting?"

Not really, particularly since your premises were lies.

"I guess you mean to say that this poor, old HIV CAN'T evolve a larger envelope to store more nucleotides."

No, I would never say anything that stupid, PaV. Envelopes are membranes--they don't evolve. The limit in packaging is the structure of the capsid, not the envelope.

" Well, if it can't do that--given that it already has a gene for the envelope,"

It doesn't have "a gene for the envelope," it has a gene that encodes a membrane protein that ends up in the envelope. It has nothing to do with packaging, and you're a lying idiot.

Zachriel said...

PaV: "Darwin said of his Origin of Species that it was a long, extended argument. So, I guess the Origin of Species ought to be ignored as well. Apparently it doesn't qualify as science either."

Smokey: "Nope. It contained all three--hypotheses, predictions, and data."

Quite so. Let me add that Darwin had circumnavigated the globe collecting biological and geological evidence, and published a very large number of papers, any number of which would have established his reputation as a scientist of the first rank; work on barnacles (Cirripedia), corals (Anthozoa), orchids (Orchidaceae) and their fertilizing insects, the formation of soil by earthworms (Oligochaeta), fertilization in flowers, geology of the Galápagos, and very much more.

art said...

Hi PaV,

Thanks for the kind words, and for addressing me as "art" - my very much preferred internet handle.

I'm sort of thinking that our discussion has reached a nice place for a pause - you see the points I've been making, and I get the feeling that follow-ups to your concerns would stray rather far from the focus I choose (for now) to limit myself to. This focus, of course, is Behe's EoE and why his proclamations aren't the end, or even the "edge", of evolution.

I'd say that we could explore your tangent (how do we explain the origins of the Legos) on UD, in the thread in which I broached some ideas. But that obviously ain't gonna happen. So we'll probably just have to agree to disagree on where the debate leads from our current place.

PaV said...

art:

I sensed the same "place for a pause". And I agree, it's time to simply agree to disagree. We can continue to read and reflect.

olegt:

I do understand landscapes and such; but, thank you for the extended image--it's always good to see how others are looking at things.

I would only point this out to you: when you invoke the image of "earthquakes", you're thinking of a changed environment (e.g., the jump from simian to human). But how many changed environments are there, whether it's a virus or a flower or a bee? And, the landscape you describe doesn't seem that complicated--a few mutations maybe. Most every IDer accepts NS and what would be termed "microevolution". That's certainly what we see with HIV. But, the whole issue of "macroevolution"--which I keep trying to get at---isn't what we see, even with this great replicator/mutator which can random-walk just about any old landscape. But, it doesn't really show any novelty. Changes, yes. Novelty, no. To me, that seems to be the crux of the matter.


smokey:

"Literally? No, you're simply lying. No one has ever said that literally, Darwinist or not. Do you even know what "literally" means?"

I know exactly what "literally" means. The reference to "the sky is the limit" had to do, of course, with the "evolution" of birds. But, of course, you're so filled with hate that you can't reason right.

You keep saying that I'm lying. Do you really believe that? Do you really believe that I'm not misinformed, I'm not wrong, I've not misspoken, I've not exaggerated, nothing like that---I've lied?

Well, I don't think you really believe what you're saying. In fact, I think you're lying about my supposed lying. Have you heard of projection?

In sum, I'm tired of your vulgar behavior. I don't care to have any kind of conversation with you at all. So, should I continue to post here, do me the favor of not responding. I don't have anything to say to you.

Marion Delgado said...

PaV, what Oleg is teaching you is called a "Nash equilibrium" and it's Population Ecology/Evolutionary Biology 101. Nonetheless, master it and you will be one up on "The DNA of HIV has mutated drastically" Behe.

Also, who calls HIV "Like malaria, [is] a microbe .."? It's not very much like plasmodium, now, is it, and microbe, while it's not a term used in technical papers, usually means something at least bacteria-sized. Seriously, one has to wonder whether someone who thinks it reproduces via DNA,calls it a microbe, and thinks it's like malaria (even if he's just making a population comparison) isn't actually confusing HIV with something else?

Marion Delgado said...

Smokey:

Partly for reasons you explained, I WOULD be willing to say this:

"I guess you mean to say that this poor, old HIV CAN'T evolve a larger envelope to store more nucleotides."

But I have zero reputation to maintain. ;)

It really seems to me that if PaV is maintaining either the contrary - that it can do so (with can meaning some meaningful probability) or that the fact that it can't do so somehow destroys "Darwinism," since the evolutionary biology model of a retrovirus that includes natural selection and random mutation would require it to be able to do so. When there is an obvious bottleneck for its evolution plus a demonstrated local equilibrium state, then yeah, it can't (practically) do any such outlandish thing. Although I'd be interested in where the "starting line" of life is located at. Remember, ID people get their info straight from the Designer, so if Behe or PaV say it's x, it's x. Very handy.

I am not bringing this up to tweak PaV, it reminds me strongly of the mistaken c. 1970 statement that 70% of the people that had ever lived were still alive. It really shows people can't do seat-of-the-pants calculations of populations extending over hundreds of thousands, let alone millions or a billion of years. If PaV would use more numbers and equations, PaV would say far fewer mistaken things. The same is true of Behe.

Torbjörn Larsson said...

PaV:

Here we have something that replicates faster than almost anything we know, something that mutates more than anything we know, and it still hasn't made it to the level of "life".

Describing "life" is a challenge of the order of describing "species". There is no one definition that fits all situations, so you have to pick a suitable definition and stick to it during a specific analysis.

There are of the order of 25 species conceptions out there, see John Wilkins reviews. (He champions the term "conception" for a specific concept.) Likewise, there are many conceptions of life, starting with the "NASA definition of life" in astrobiology of "replicators" moving on to more elaborate ones.

IANAB, but I champion definitions that are inspired by theory where they can be used since they correlate better with it. Wherefore I prefer to use the following modern conception of life:

An organism is the unit element of a continuous lineage with an individual evolutionary history.

The model for the definition is an organism as the current slice in a continous process. Thus combining the idea of life as individual and life as process with evolution and a robust definition of organism. Quite a few birds knocked down with a single stone.

The definition excludes organelles and such replicators as prions because they have entered dependent niches, they are subsumed into an organism. But viruses are independent organisms under the definition, they coevolve as olegt discusses.

FWIW, large viruses are easily larger than bacterias physically and genomically, and have elements of metabolism which obligate bacterias may lack.

You may prefer another definition. That however doesn't change the fact that viruses can be seen as life in some circumstances.

Mike Dunn:

You guys are wasting all this time,

Says the guy who wastes his time with contra-factual pseudoscience, dangerous pseudoscience to boot: HIV kills. You are free to express stupid opinions, but please do that where it is appropriate.

Hermagoras said...

Hey Mike,

Nice to see you again. Smokey suggested a bet with you a while back. Want to take it up?

H

Smokey said...

PaV wrote:
"I know exactly what "literally" means. The reference to "the sky is the limit" had to do, of course, with the "evolution" of birds."

Literally, you're wrong about that, too, as the sky isn't the limit for birds. Penguins are the best example of that.

"But, of course, you're so filled with hate that you can't reason right."

You're projecting.

"You keep saying that I'm lying. Do you really believe that? Do you really believe that I'm not misinformed, I'm not wrong, I've not misspoken, I've not exaggerated, nothing like that---I've lied?"

Yes. For example, when you falsely accused me of misquoting Behe, when you were corrected, you didn't retract a thing.

"In sum, I'm tired of your vulgar behavior."

Well, I'd say it's far more vulgar, even obscene, to claim from a position of ignorance that a deadly virus is "simple" than it is to call someone a cottage cheese dripping pussy.

"I don't care to have any kind of conversation with you at all."

We haven't been conversing. You've been lying, and I've been pointing out your lies.

"So, should I continue to post here, do me the favor of not responding."

No way.

"I don't have anything to say to you."

So what?

Hermagoras said...

PaV,

I've read your latest on ERV at Uncommon Descent. I can't post there, as I've been banned. But I thought I'd respond to this:

"ERV’s basic challenge–although it wasn’t formally accepted as such on her blog–is that, contrary to what a.) Behe says in EoE, and contrary to what he should clearly have been aware of, b.) HIV presents an example of multiple protein-to-protein binding sites (4) in c.) much less the number of replications in a CCC (10^20), thus d.) falsigying [sic] Behe’s claims."

If "basic challenge" refers to ERV's first post on the subject, then No. That was not her "basic challenge." As you point out, she didn't even say that on her blog. It was not her point. Her point was addressed to a specific moment in an interview where Behe repeats something that is easily shown to be wrong. This moment in the interview leads ERV back to the same claim in the book (that HIV's "basic genetics have changed little in the last decades," Figure 7.3). It is that claim which she shows to be wrong.

She's not showing that the whole book is wrong (though her findings have implications for the whole). She is showing that, where Behe's claims interact with her area of expertise, Behe is wrong.

This is, of course, highly amusing, as Behe's the expert, and ERV is "just" a graduate student. It makes one wonder what other broad and unsupported claims are in the book.

While I have your attention, will someone at UD point out that Sal's accusation that ERV was being dishonest is wrong? I have asked others to do this, but nobody's taken me up on it. Retractions are demanded here and in subsequent comments. No? You going to let that stand? Or are you going to live up to UD's oft-stated, but rarely realized, reputation for probity?

H

Marion Delgado said...

Torbjörn Larsson:

I am trying to sum up what PaV should know to fix his misunderstandings, I'd be interested in your take:

1. He should take Behe's sloppiness (DNA/RNA, microbes, no changes in HIV) more seriously, and disregard some of his qualitative statements (such as how much evolution is evolution, and good enough to be life).

2. He should realize you can't just guesstimate populations of anything over time, you need to calculate them. That would give him a better sense of the time needed, too.

3. He should understand landscapes and Nash equilibriums better, and why populations stay at local equilibriums instead of finding an abstract best fit for a given environment. This also aids the sense of the time needed.

It's a little sloppy of me to say microbes are bacteria-sized when as you pointed out, some viruses are bigger than some bacteria, but the "like malaria, a microbe" still bugs me. It's unhelpful - there are, what 650 million infected with malaria? He could have said, the count of individual HIV is more per victim than of plasmodium in malaria victims, so the total count of HIV approaches that of malaria organisms - no idea if that's true or meaningful.

Taking PaV as a paradigm Behe supporter, do you think this ought to be a sufficient list?

Ian Musgrave said...

PaV wrote:Here's the link to an article that is looking at the similarity between Vpu and the M2 gene of Type A Influenza.

Functional similarity only in this paper. Vpu and M2 are structurally similar to the extent that "A hydrophobic N-terminal anchor is followed by a very hydrophobic C terminus, with at least 18 charged residues in each case." Klimkait et al. 64 (2): 621. J Virol. (1990). In terms of sequence, there is no significant sequence similarity between M2 and Vpu (sequences and alignments on request).

And it turns out that the conclusion of the paper you cite is that Vpu, while a cation channel, is not a proton channel like M2 (pg 7115):
It would seem, therefore, that Vpu channels are unlikely to be functionally analogous to the M2 and NB channels of the influenza viruses.

PaV: It would be easy, I think, to simply suppose that somewhere along the line that SIV picked up the M2 from a chimp that was infected with Type A Influenza.

Easy, but dead wrong. A) SIV Vpu is not a viroporin, the viroporin activity appeared only after HIV had infected humans for some time (remember this timeline. B) SIV Vpu and M2 viroporins share no significant sequence similarity. C) M2 viroporin and HIV-1 Vpu viroporins share no sequence similarity either; it is very unlikely that Vpu is a modified M2 in any form.

PaV: The fact that the 'ion channel' seems to form spontaneously minimizes any supposed complexity that we want to attribute to Vpu on the basis of its forming a viroporin.

It’s not complexity per se (but lots of proteins form structures spontaneously, from ion channels to the viron capsids themselves to flagella, the fact that it occurs spontaneously doesn’t mean it’s not complex), but the fact that Vpu has gained an entirely new function. Vpu is not a viroporin in SIV, HIV-1 class O or HIV-1 Class N viruses, it is only a viroporin in HIV-1 class M viruses.

So, during it’s stay in humans, HIV-1 Vpu has gained a new protein-protein binding site that allows it to form a viroporin, it has also gained a binding site that targets it to the Golgi apparatus (this isn’t present in SIV or early HIV-1 strains). Also, in the 60’s Vpu gains a membrane targeting sequence in the HIV-1-M C subgroup.

To summarize, since HIV has infected humans, HIV-1 has gained a minimum of 3 protein-protein binding sites (I’m ignoring a new Casein Kinase II binding site and there is probably also a new ion gating site as well in HIV-1-M C). In the "Edge of Evolution", Behe states a couple of times quite unequivocally, that HIV has developed no new binding sites (eg See page 143 and figure 7.4, page 144 of EoE, where Behe shows HIV having 0 new binding sites). So, Behe is dead wrong about HIV, and that is just looking at one HIV protein, let alone the rest of the HIV proteins. What else is he dead wrong about?

Torbjörn Larsson said...

Marion Delgado:

Oh ancient and wise one (251 years without once being stoned (no, not that way), hanged or shot to death - I'm duly impressed :-P), alas IANAB ("I'm not a biologist").

But FWIW:

1. Over on The Panda's Thumb, IIRC under ERV's post, I too commented on Behe's and others "microbes" (as applied to viruses) but a biologist claimed that is fair use. It covers malaria too AFAIK. But I agree on your general point.

3. You could also add ERV's point about ERVs as a cloud of a quasispecies (there is a post here somewhere with a nice graphics) which have a hard time to localize enough for a more or less local "best" fit anyway. That depends on how much detail you want to dilute the message with, of course.

I'm afraid I can't come up with more points, tho'. (It's late here.) Fortunately, those are already forceful and relevant ones.

And yes, a person in full denial as PaV can not really learn anything useful. A short and powerful list should show observers (as in fence-sitters) who is right. And hopefully be something that could tip a denialist with cognitive dissonance over to the light side eventually.

Um, Ian Musgrave's question (what else is Behe wrong about) should probably also be in there.

Smokey said...

Over on UD, PaV has terminal cognitive dissonance:

"The argument Behe makes in EoE deals exclusively, and consistently, with eukaryotic cells. Viruses aren’t even classified as “life”."

Um...then why does Behe bring up HIV at all?

Torbjörn Larsson said...

[Making 2nd rounds, no more ideas than last time.]

Smokey, quite a find, and perhaps something to add to the list.

We can only hope his weakened versions of infectious reality memes mutate to give a mind-to-fact binding site before his denialist immune system rejects them.

PaV said...

Ian Musgrave wrote:

“PaV wrote: Here's the link to an article that is looking at the similarity between Vpu and the M2 gene of Type A Influenza.”

IM: Functional similarity only in this paper. Vpu and M2 are structurally similar to the extent that "A hydrophobic N-terminal anchor is followed by a very hydrophobic C terminus, with at least 18 charged residues in each case." Klimkait et al. 64 (2): 621. J Virol. (1990). In terms of sequence, there is no significant sequence similarity between M2 and Vpu (sequences and alignments on request).

It’s interesting that you include just this quote. The sentence before this quote reads:
“For example, the size, hydropathicity, and domain structure of the membrane-
associated influenza virus M2 protein (15, 26) and the foot-and-mouth disease virus protein p3A (5) are strikingly similar to those of vpu (Fig. 10).”

Well, which is it? “No significant sequence similarity”, or “strikingly similar”? Yes, they have the nucleotide sequence of vpu in the paper, but I didn’t find any sequence for M2. (But more on this later)

IM: And it turns out that the conclusion of the paper you cite is that Vpu, while a cation channel, is not a proton channel like M2 (pg 7115):

It’s a 1996 paper. But on the same page as your quote (7115) we find another quote that seems very germane to the conversation taking place here. It is as follows:
“On the other hand, like M2, Vpu is found in the Golgi and
endoplasmic reticulum membranes
.”


“PaV: It would be easy, I think, to simply suppose that somewhere along the line that SIV picked up the M2 from a chimp that was infected with Type A Influenza.”

IM: Easy, but dead wrong. A) SIV Vpu is not a viroporin, the viroporin activity appeared only after HIV had infected humans for some time (remember this timeline.

But, of course, that is part of the point I’ve been making: namely, that once SIV entered humans that some kind of switching took place between type A influenza and SIV, resulting in what we know as HIV-1. From the article you quoted, we read:
“It remains to be shown whether these two primate lentiviruses utilize another viral protein to functionally replace vpu.”

IM: B) SIV Vpu and M2 viroporins share no significant sequence similarity.

I don’t see the relevancy. It only enhances the likelihood that some kind of “replacement” has taken place in HIV-1.

IM: C) M2 viroporin and HIV-1 Vpu viroporins share no sequence similarity either; it is very unlikely that Vpu is a modified M2 in any form.

At UD, I linked not only the article you’ve mentioned, but one other. In that other article, the authors state: “Taken together, these results indicate for the first time that the TM domain of the Vpu protein can be functionally substituted with the TM of M2 of influenza A virus.”

This only shows that they can substitute for each other. But what about similarity?

Here’s another article: “A single amino acid substitution within the transmembrane domain of the human immunodeficiency virus type 1 Vpu protein renders simian-human immunodeficiency virus (SHIV(KU-1bMC33)) susceptible to rimantadine.”

They say this: “These data indicate that the Vpu protein of HIV-1 can be converted into a rimantadine-sensitive ion channel with the alteration of one amino acid . . .”

Rimantadine shuts down the M2 proton pump. Again, this is very suggestive of vpu-hiv-1’s origin, and of its similarity to M2. Remember that Behe’s CCC involved TWO amino acid substitutions, not just ONE.


“PaV: The fact that the 'ion channel' seems to form spontaneously minimizes any supposed complexity that we want to attribute to Vpu on the basis of its forming a viroporin”.

IM: It’s not complexity per se (but lots of proteins form structures spontaneously, from ion channels to the viron capsids themselves to flagella, the fact that it occurs spontaneously doesn’t mean it’s not complex), but the fact that Vpu has gained an entirely new function. Vpu is not a viroporin in SIV, HIV-1 class O or HIV-1 Class N viruses, it is only a viroporin in HIV-1 class M viruses.

Yes, but as the previous quote indicates, is it only ONE amino acid away from such a new function?

IM: So, during it’s stay in humans, HIV-1 Vpu has gained a new protein-protein binding site that allows it to form a viroporin, it has also gained a binding site that targets it to the Golgi apparatus (this isn’t present in SIV or early HIV-1 strains). Also, in the 60’s Vpu gains a membrane targeting sequence in the HIV-1-M C subgroup.

The protein-protein binding site that Behe discusses in EoE is a binding site that involves both proteins changing. Here, only the vpu protein changes. But leaving that to the one side, if some kind of “replacement” event has taken place in vpu gene during the transition from simians to humans, specifically, M2 being substituted for the vpu originally found in SIV, then ONE amino acid change can bring about its viroporin activity. IOW, there is NO need for a protein-protein binding site to develop. As well, there is the quote above: “On the other hand, like M2, Vpu is found in the Golgi and
endoplasmic reticulum membranes.
” Does this mean that vpu has acquired its targeting to the Golgi bodies from M2 as well.



IM: To summarize, since HIV has infected humans, HIV-1 has gained a minimum of 3 protein-protein binding sites (I’m ignoring a new Casein Kinase II binding site and there is probably also a new ion gating site as well in HIV-1-M C).


It would seem that until such time as a link between vpu origination in HIV and M2 hybridization into HIV-1 can be definitively ruled out, we should hesitate in declaring how many “novelties” we find in vpu.


IM: In the "Edge of Evolution", Behe states a couple of times quite unequivocally, that HIV has developed no new binding sites (eg See page 143 and figure 7.4, page 144 of EoE, where Behe shows HIV having 0 new binding sites). So, Behe is dead wrong about HIV, and that is just looking at one HIV protein, let alone the rest of the HIV proteins. What else is he dead wrong about?

Sal Cordova, from the very beginning of the discussion that took place at UD, made clear the distinction between the “kinds” of protein-protein binding sites that Behe was talking about and the ones that are being alleged to have arisen in HIV-1. I just point this out. I think a clear and sober reading of what Behe has written (and including his quote in World Magazine) makes this distinction abundantly clear.

As I’ve written over at UD, the fact that Darwinists are grasping at the evolutionarily insignificant changes that a less-than-life virus (possibly) demonstrates can only be taken as a sign of how desperate they are in the face of Behe’s unassailable attack on the limits of NS.

Marion Delgado said...

Behe is far beyond where a "clear sober" reading would cause anyone to agree with him. Soon, he'll be past where his convoluted, dishonest, ass-covering and obfuscating rhetorical-flourishes-masquerading-as-scientific-argument nonsense will bear sober reading of any kind.

Indeed, the only remaining question will be what to drink to read Behe.

"Behe before liquor, never sicker."

Marion Delgado said...

And PaV:

We're not Darwinists - or even Galtonists. Or Gouldists. Or whatever-person-ists. That's cheapjack right-wing framespeak. Capisce?

Indeed, you are much closer to being a Beheist - in the sense that excuse-making colleagues and followers in the former Soviet Union were Lysenkoists - than we are to being "Darwinists."

Compare:

If DARWIN got something wrong, WE say:

"Who cares, it was a long time ago and Darwin is not the last word on anything."

(Indeed, what morons you Beheists are to think that if, say Wallace, or Wallace and Galton or ... had advanced natural selection it would have made any difference whatsoever. But that's how you think. You think everything is a matter of faith, cultism, and personalities, and it's more important to you that you like or admire someone than that they be CORRECT. Which is all we give a damn about.)gf

if BEHE gets something wrong, YOU say:

Dr. Behe is right but you are making the typical mistake of assuming words in English mean the things they mean in dictionaries. And that scientific papers mean what they say in abstracts. Typical.

OR

Well, Dr. Behe misspoke, but it's irrelevant.

From now on PaV, I am simply going to ALWAYS use "you Beheists" whenever I refer to anything you say in comments.

PaV said...

Mario:

This is what Behe writes on p. 34:

"In this book we are concerned with how machinery can be built. To build a complex machine many different pieces have to be brought together and fitted to one another."

Is that plain English enough for you? So, when Behe says that there is no biochemical novelty in HIV, this is his take-off point. The only thing that comes close to fitting into this point of view when it comes to HIV and the points that ERV has made is that of the ion-channel. But as my argument above makes clear, the M2 gene might easily have been, let us say, "co-opted" by HIV, and can explain many of the new workings of the vpu protein.

ERV said...

PaV-- You are making an argument equivalent to "fruit flies got wings from 'co-opting' blue whale fins".

Please read my post 'Viruses are not Magic', and if you are still not convinced, please explain to me how this 'easy' co-option occurred, biochemically. Its 'easy', right?

Id also like you to recognize what you just did. Heads you win, tails we lose. Behe drew a line in the sand 'This is possible, this is not'. Its on the inside cover of that god forsaken book. And HIV crossed that line. NOW you say that the line needs to be drawn 5 feet away from where it was drawn before-- Oh, and we're 'desperate' and 'pathetic' for pointing out HIV crossed the first line in the sand.

'You' can never be wrong. Do you recognize that?

PaV said...

ERV:
"PaV-- You are making an argument equivalent to "fruit flies got wings from 'co-opting' blue whale fins"."

I'm suggesting that one virus picks up and uses a gene from another virus. You're comparing that to a 'sharing' of a variety of genes from two completely different phyla. I don't see that the comparison is apt.


ERV:
"Please read my post 'Viruses are not Magic', and if you are still not convinced, please explain to me how this 'easy' co-option occurred, biochemically. Its 'easy', right?"

From the thread you mentioned:

"Viruses are not magic. They are not a singular entity.

Influenza-- Segmented negative strand RNA virus, infects airway epithelial cells through endocytosis, needs RNA dependent RNA polymerase

HIV-1-- Double-stranded retrovirus, infects CD+ T-cells (eh, some other immune cells) through membrane fusion, needs reverse transcriptase

Square Peg. Round hole. These guys arent going to be swapping genes. Unless we do it."


If someone has the flu, wouldn't you expect their T-cells to attack the flu? So, if the T-cell with the HIV attached comes into contact with cells in the airway that contain the flu virus (and, it so happens, that the genes of Type A Influenza are all single RNA strands, i.e., independent of each other) we now have the round hole touching up against the square peg. And, IIRC, HIV is known to incorporate genes from one subtype into the other, so why can't it incorporate the single gene strand for the M2 protein. This would seem to be a plausible enough mechanism.

ERV:

"Behe drew a line in the sand 'This is possible, this is not'."

I think all of this revolves around trying to properly understand Behe's argument in EoE. Why is this unfair?

You and Ian have suggested the development of a number of "protein-protein binding sites" that have arisen in HIV, contrary to what Behe stated in his book. It seems to me that the starting point in answering that challenge is to make sure that, indeed, these putative P-P Binding sites have arisen as a novelty. Next, to ascertain whether they fall into the type of biochemical change within the organism itself that Behe addressed himself to. And then, finally, to determine whether this in anyway invalidates his CCC number. (As I've already pointed out, one in 10^20 in a eukaryote is not equivalent to one in 10^20 in a virus)

We're basically at still at step one here.

Let me add, there are two possibilities to be considered: (1) that M2 has been incorporated into HIV-1 somewhere along the line, and (2) that a "single amino acid" substitution is sufficient to give rise in vpu to the same TM properties as M2. (Here's the abstract.)

Obviously if a "single" a.a. substitution can facilitate the development of these new properties of vpu, then we're dealing with something much less even than a CCC.

Ian Musgrave said...

PaV wrote:
IM: B) SIV Vpu and M2 viroporins share no significant sequence similarity.

I don’t see the relevancy. It only enhances the likelihood that some kind of “replacement” has taken place in HIV-1.


This shows definitively that HIV Vpu is not a “swapped” M2. If there was “replacement”, then there would be no sequence similarlity between SIV Vpu and HIV Vpu, and HIV Vpu would be similar to M2, its ancestor. But we see the opposite, SIV and HIV Vpu’s are obviously (and satistically) similar, and HIV Vpu has no similarity to M2

IM: C) M2 viroporin and HIV-1 Vpu viroporins share no sequence similarity either; it is very unlikely that Vpu is a modified M2 in any form.

At UD, I linked not only the article you’ve mentioned, but one other. In that other article, the authors state: “Taken together, these results indicate for the first time that the TM domain of the Vpu protein can be functionally substituted with the TM of M2 of influenza A virus.”


Functional substitution by itself does not mean that the proteins are derived from each other. We have several examples where proteins with different evolutionary histories and sequence can end up with similar functions. Trypsin and Subtilisn, Northern and Southern hemisphere antifreeze proteins. There is several ways you can build short helixes, and the fact that you can get short helixes assembling into ion channels is not evidence that they are evolutionarily derived from one another.

Let’s re-iterate that. Because things have the same function does not mean that they are derived from each other.

They say this: “These data indicate that the Vpu protein of HIV-1 can be converted into a rimantadine-sensitive ion channel with the alteration of one amino acid . . .”

Rimantadine shuts down the M2 proton pump. Again, this is very suggestive of vpu-hiv-1’s origin, and of its similarity to M2.


Please read for comprehension. In this experiment, they gave an existing ion channel the drug sensitivity of a different ion channel (by a single amino acid substitution). It has no bearing on the origin of Vpu.

The Factician said...

As I've already pointed out, one in 10^20 in a eukaryote is not equivalent to one in 10^20 in a virus

Do viruses use a different math than we do?

Ian Musgrave said...

PaV wrote: IM: B) SIV Vpu and M2 viroporins share no significant sequence similarity.
I don’t see the relevancy. It only enhances the likelihood that some kind of “replacement” has taken place in HIV-1.


Now, this is an example where you can actually test the hypthoesis. Lets state PaV’s hypothesis clearly:
“The Vpu of HIV-1 class M is an M2 protein swapped in after SIV crossed to humans becoming HIV.” It also has to come in after HIV-1 O and HIV-1 N, as these are not viroporins either.

So as a result of PaV’s hypothesis we can make clear predictions, if PaV is right:
1) HIV Vpu should have greater sequence similarity to Influenza A M2 than to SIV Vpu and
2) HIV Vpu and Influenza A M2 should form an nested phylogeny as an out-group to SIV Vpu and HIV-O and HIV-N Vpu

Well, I went ahead and tested this. Blasting individual M2’s against individual Vpu’s pair wise came up with no significant sequence similarity. I was using a variety if serovars from human, pig and bird isolates (at least 3 from each serovar, I could find no recorded chimp influenza isolates). Blasting individual M2’s against all retroviral proteins returned no significant sequence similarity either (whereas blasting any given Vpu against all retroviral protein successfully pulled up all Vpu’s). Inspection of several aligned sequences form SIV, HIV-), N and M clearly shows that these are related sequences, while the aligned M2 sequences are clearly different (there is a highly conserved 12 aa sequence at the C terminal in the Vpu’s which is completely absent from M2 for example). So we can consider prediction 1 falsified.

Since there was no significant sequence similarity, I couldn’t use the NLM ree view, so I forced a phylogeny through the MAFF server. The phylogeny clearly shows M2 as an out-group to the Vpu’s, with HIV nesting within SIV. So prediction 2 is falsified.

(alignments and trees available on request, but the sequence stuuf can be done by anyone via NCBI, just search on “influenza A AND M2” in protein, then follow the BLAST link and paste the GI number of the appropriate M2 protein into the BLAST search field. )

Conclusion: HIV-1 M Vpu is a descendent of SIV Vpu, and is not related in any way to the M2 viroporin.

Now, PaV, you could have tested your hypothesis yourself, but you didn’t. We had to go and do it for you. Now, do you accept that the Vpu viroporin activity is not “swapped in” from M2? (and No, a one amino acid change which changes the drug sensitivity of an ion channel is not the same as generating an ion channel de novo.

Torbjörn Larsson said...
This comment has been removed by the author.
Torbjörn Larsson said...

PaV:

I think all of this revolves around trying to properly understand Behe's argument in EoE.

Oh, we understand Behe's argument: "Evolution is wrong, therefore creationism." On top of this elementary error of false choice he publishes a popular book instead of research results. In an old and reliable science no less.

To point out his errors therefore seems superfluous, but some people needs to be shown every detail that pegs Behe as a buffoon.

To date Behe has in Edge of Evolution:

1. Claimed that intraflagellar transport is universally required for cilium construction. But at least one apicomplexian lacks IFT genes.

2. Used malaria as the biggest running EoE example. But the apicomplexian that lacks IFT genes is Plasmodium falciparum!

3. Claimed that HIV hasn't evolved new biochemical functions. But there are a lot of those.

4. Claimed unequivocally that HIV hasn't evolved new binding sites. But there are a lot of those.

5. Claimed, together with one commenter PaV, that HIV contains DNA. But it is an ssRNA-RT virus.

So the question remains - what else is Behe ignorant and dead wrong about?

Ian Musgrave said...

PaV, just a note about the perils of putting your faith in functional similartity. As part of my postdoc I worked on ion channels. Ligand gated channels, voltage gated channels and Transient Receptor Potentiated (TRP) channels (I’m a pretty good hand at measuring almost any intracellular ion in cells, even obscure ones like Sf9 embryonic insect cells). At one point I characterized the ion entry through Maitotoxin channels (my Maitotoxin paper is my all time highest cited paper). Functionally, Maitotoxin channels looks a heck of a lot like TRP channels in terms of ion density carried and selective blockade, but structurally they are nothing like each other. So, take home message, functional similarity is no guarantee that the structures are related. While I have demonstrated the M2 and Vpu are not related, it’s worthwhile to keep this lesson in the back of your mind when you encounter other proteins with similar functions.

PaV said...

Ian Musgrave:

“Now, PaV, you could have tested your hypothesis yourself, but you didn’t. We had to go and do it for you.”

Ian, it’s you who are making the claim against Behe, not me. And not everyone is a virologist with the kinds of resources that you have at your fingertips. I post from my living room, not a lab.

Ian Musgrave:

“Now, do you accept that the Vpu viroporin activity is not “swapped in” from M2?

Yes, I do.

We can drop that thesis. Another thesis might be this: that the immune system of simians has a way of interrupting the “ion-channel” the vpu forms in humans. Now, looking at one of ERV’s previous posts, it appears that there’s substantial difference between SIVcpz vpu and HIV-1 vpu, so it would seem to be more than that.

One thing seems quite clear as one reads what little is publicly available, mostly abstracts (again, not everyone has the resources available that you take for granted), and that is that the N-terminal domain (“ion-channel”) and the C-terminus domain (CD4 degradation) have distinct, different functions. So the U protein serves two functions. There’s also the notion of vpu being directed to the Golgi bodies, and the two casein kinase binding sites for CD4 degradation.

Well, what are we dealing with? It’s been shown, using one of ERV’s citations, that a simple serine insertion along a string of a.a. can duplicate the function of the second casein kinase binding site. This is a single a.a. event. The Golgi signal involves the LRLL motif; that’s four a.a.’s. But there’s a fair likelihood that one of the L’s is already present, so then we might only be dealing with a three a.a. event. Then we have the “ion-channel”, which might require a number of a.a. changes. Remember that a single a.a. mutation changed a normal functioning SHIV TM into one resistant to rimantidine. So, are we dealing with one, two, or three a.a.’s? It’s a guess. And, contrary to what ERV has said, this doesn’t constitute a protein-to-protein binding; it’s a simple oligamerization of the U protein. So, we’re dealing with perhaps as many as four different events, involving perhaps as many as three a.a.’s, and possibly, in one case, four.

Well, how many replications are needed for something like that? Every ten HIV-1 viruses contains one nucleotide substitution. To get a substitution at just the right spot requires, on average, 10^5 viruses, given its 10^4 genome size. Now let’s assume that of the three nucleotides needed, one is silent. We then need (10^5)^4=10^20 replications.

What is the replication rate of HIV-1. It is of the order of 10^10 viruses per infection cycle, with an infection cycle taking 1.5 days. (see here). Now the reference I’ve cited says that the replication rate could be up to 30 times higher. Let’s just stick with 10^10/1.5 days. That’s 2.4 x 10^12 viruses/person/year. It took, based on your phylogeny, 30 years for the LRLL sequence to develop. Let’s assume only a million people infected. What are the numbers? 30 x 2.4 x 10^12 x 10^6=7.2 x 10^19. And, if we assume the higher replication rate? It’s 30 x 7.2 x 10^19 = 2.2 x 10^21, which gives us 10^20 replications in 1.5 years. Well, what’s the big deal?

Yes, the “ion-channel” appears; but it is a “self-assembled” TM unit. Yes, CD4 degradation involves another binding site. Yes, vpu now goes to the Golgi body. But all of this can be accounted for using simple genetic calculations.

Now, if we take a giant step back, then we have to say to ourselves, here is an organism that has replicated itself 10^20 times and we see at most four a.a. changes, and no NEW biochemistry. Yes, HIV-1 acts differently, and in sometimes a new way in relation to the host cell but it hasn’t changed the way in which it interacts with itself.

As Behe rightly puts it: “Yet all those mutations, while medically important, have changed the functioning virus very little. It still has the same number of genes that work in the same way. There is no new molecular machinery.”

Is there something Behe should be apologizing about?

Ian Musgrave said...

Pav wrote: ..not everyone is a virologist with the kinds of resources that you have at your fingertips. I post from my living room, not a lab.

Actually, I used only publicly available resources from my home computer. Anyone can do sequence alignments using Pubmed Being Australian, I have only dodgy access to broadband, on a less than spectacular computer, so if I can do it from home, anyone can. (MAFF is a bit more obscure, but it is still a public access service). My wife is only mildly puzzled these days to find our computer littered with sequence alignments (and STEREO satellite images fro comet hunting).

The Golgi signal involves the LRLL motif;

No, that’s the plasma membrane targeting motif in the HIV-1, M-C subtype, the Golgi sequence is ESGNES.

Then we have the “ion-channel”, which might require a number of a.a. changes. Remember that a single a.a. mutation changed a normal functioning SHIV TM into one resistant to rimantidine.

No need to put the ion channel in scare quotes, Vpu is an ion channel. And you keep on banging on about the rimantidine sensitivity. That is irrelevant to the conversion of SIV Vpu to the HIV-1-M-C ion channel Vpu (as it converts and ion channel into a drug sensitive ion channel). You cannot derive the number of aa changes required to form an ion channel from drug sensitivity acquisition.

And, contrary to what ERV has said, this doesn’t constitute a protein-to-protein binding; it’s a simple oligamerization of the U protein.

That has to take the cake as one of the most breathtakingly silly statements I have heard in a while. How does Vpu (a protein) oligamerise, through protein-protein binding! (how do you think proteins oligamerise?)

Yes, the “ion-channel” appears; but it is a “self-assembled” TM unit. Just like the nicotinic channel, the TRP channel and the bacterial flagellum (mix a bunch of isolated flagellar bits in a test tube and the spontanousl self assemble into at TM channel, I can imagine why you think self assembly has any relevance to protein-protein binding issues).

es, HIV-1 acts differently, and in sometimes a new way in relation to the host cell but it hasn’t changed the way in which it interacts with itself.

And WHOOSH! The goes those goal posts. Sheesh.

PaV said...

Ian Musgrave:

“Being Australian, I have only dodgy access to broadband, on a less than spectacular computer, so if I can do it from home, anyone can.”

I’ll have to try it. Hopefully my computer won’t crash.

Ian Musgrave:

You cannot derive the number of aa changes required to form an ion channel from drug sensitivity acquisition.

So, then, we’re left to a complete guess. But the point in mentioning the single aa substitution was that just one aa substitution had a significant effect on the TM.

Ian Musgrave:

“PaV: And, contrary to what ERV has said, this doesn’t constitute a protein-to-protein binding; it’s a simple oligamerization of the U protein.”

IM: That has to take the cake as one of the most breathtakingly silly statements I have heard in a while. How does Vpu (a protein) oligamerise, through protein-protein binding! (how do you think proteins oligamerise?)

Well, Ian, maybe if you had been paying attention, you might have remembered just exactly what Behe was talking about when he described a “protein-to-protein binding site”. Here’s p.131: “So we can ask, how difficult would it be for two proteins that initially did not bind to each other to develop a strong, specific interaction by random mutation and natural selction?” Did you notice the word “two”? Vpu is vpu. That’s ‘one’ protein, not ‘two’. This is the problem with this entire discussion. Later on you’ll say the goalposts have been moved. No, the goalposts haven’t moved, they’re just being properly assessed. You either consciously or unconsciously misunderstand Behe, and then attack the strawman.

Ian Musgrave:

PaV: “ HIV-1 acts differently, and in sometimes a new way in relation to the host cell but it hasn’t changed the way in which it interacts with itself.”

IM: And WHOOSH! The goes those goal posts. Sheesh.

Yes, they’ve been put in their proper position----at last!

Smokey said...

PaV wrote:
"I’ll have to try it [aligning sequences]. Hopefully my computer won’t crash."

An honest person would have graciously admitted that the claim, "And not everyone is a virologist with the kinds of resources that you have at your fingertips. I post from my living room, not a lab," was wrong.

But not you! You just move those goalposts! You should have tried to align the sequences before making your laughable claim.

"So, then, we’re left to a complete guess."

No, we aren't.

"But the point in mentioning the single aa substitution was that just one aa substitution had a significant effect on the TM."

Anyone who has taken the absolute lowest-level biochemistry class understands this. You are illustrating the problem with Behe's simplistic attempts to quantify using only numbers of aa residues.

"Well, Ian, maybe if you had been paying attention, ..."

We are paying attention, PaV. We are laughing at your desperation.

"...you might have remembered just exactly what Behe was talking about when he described a “protein-to-protein binding site”."

But that's not what biochemists mean when they discuss protein-protein binding sites, so it's just a case of goalpost-moving.

"Here’s p.131: “So we can ask, how difficult would it be for two proteins that initially did not bind to each other to develop a strong, specific interaction by random mutation and natural selction?”"

No easier or more difficult than it would be for a single protein to evolve to become a homodimer, or a homo-anything-mer. No difference at all.

Moreover, Behe is fudging furiously, because most of the protein-protein interactions that appear to be specific in vivo turn out to be only selective in vitro, or in overexpression experiments in vivo. It's a major problem predicted by evolutionary theory, but anathema to intelligent designers. That's why Behe is fudging it. In fact, proteins love to interact with each other; that's why so few of them are soluble in physiological solutions. If you disagree, simply list 50 biological proteins >150 aa residues that are soluble in aqueous solution. I'll spot you two:

serum albumin
keyhole limpet hemocyanin

"Did you notice the word “two”?"

BWAHAHAHAHA! That's what you're reduced to? Claiming that the notion of evolving a protein-protein interaction doesn't apply in any way to homomultimers?

"Vpu is vpu. That’s ‘one’ protein, not ‘two’."

But homodimerization involves two different parts of Vpu, so the "evolutionary difficulty" is no different. Behe's distinction is meaningless, but it's all you have left, I guess.

"This is the problem with this entire discussion. Later on you’ll say the goalposts have been moved. No, the goalposts haven’t moved, they’re just being properly assessed."

Point me to another biochemist who claims that the evolution of homomultimers is more or less likely than the evolution of heteromultimers, then.

"You either consciously or unconsciously misunderstand Behe, and then attack the strawman."

No, we clearly understand Behe's dishonesty and the rhetorical tricks he uses to fool dilettantes like you, and we attack his falsehoods and misrepresentations.

There's a reason why Behe has never responded to ERV, you know.

PaV said...

I refuse to respond to anything Smokey writes. I've asked him to please not comment on anything I post here. I renew the request.

Smokey said...

Sit on the ends of those goalposts instead of carting them around, PaV. You're not responding because you don't have a coherent response.

Ian Musgrave said...

PaV wrote: Did you notice the word “two”? Vpu is vpu. That’s ‘one’ protein, not ‘two’.

That is so mind bogglingly silly it takes my breath away even more than your last statement. The amino acid changes and interactions required for two molecules (notice that “two” not one) of Vpu to bind to each other is exactly the same as the amino acid interactions required for Vpu to bind to the Golgi apparatus or Vpu and the plasma membrane. If fact it is more, one molecule of Vpu is required to bind two molecules of Vpu in the correct orientation to form the core of the eventual penatmer that makes the ion channel. Not the correct orientation bit, any old binding won’t do, there is a very restricted range of binding sites that produces a pentamer with a central pore of the right shape and size to be an ion channel.

Okay, lets restate that, one molecule of HIV-1M Vpu binds two separate molecules of HIV-1M Vpu specicially to form a multimolecular complex with a new function, being an ion channel. HIV-1 O and HIV-1-N Vpu’s are monomers that do not form multimolecular complexes and have no ion channel function.

This development of a protein-protein binding site in HIV in historic times completely fulfils Behe’s requirements, and so falsifies Behe’s claim that zero protein protein binding sites have developed in HIV since it infected humans.

PaV, think carefully if you wish to insist on ruling out any homo-oligomers as exaples of protein-protein binding (no protein biologist is going to agree with you), because you have just ruled out the bacterial flagellum as an example of complexity. Over 95% of the bacterial flagellum is homo-oligomer binding (Most of the flagellum is FliC binding to FliC, then there is FlgE-FlgE, FlgL-FlgL etc). But if you wish to insist that the Flageullum isn’t an example of complexity, who an I to argue with you?

art said...

PaV, here's the exercise - start with one polypeptide chain that does not form dimers or oligomers. Then ask - how many protein-protein binding sites in this protein (not amino acid changes - Behe talks about binding sites, and so will we) do you need to turn this protein into one that can form homodimers?

How many (minimum will do fine) are needed to produce, from this single monomeric protein, something that can form pentamers?

Once you finish this exercise, you will understand why Ian, and ERV, and Smokey, and everyone else here are accusing you of moving goalposts. The issue is protein binding sites, places where two different polypeptide chains (and they are different chains, even if they have the same sequence - if they were not different, there would only be one subunit) must interact. The fact that Vpu forms pentamers means that at least two "CCC"'s appeared from out of the blue.

Also, your claims that HIV in some way can handle the probabilities better than other organisms makes no sense. Ian has explained on PT how the "probabilistic resources" available to HIV do not even come close to those Behe insists are needed to make two "CCC"'s. It's fantabulous fertility (can a virus be fertile??) doesn't rescue Behe in this regard.

art said...

More about protein interactions, homo- vs heteroligomers, etc.

Pav, I suspect that you are trying to argue that, because Behe did not explicitly speak about homo-oligomers in the EoE, examples of interaction sites involving homo-oligomers are not valid counterpoints to Behe’s claims. This doesn’t make any sense to anyone who works with protein interactions. I’ll try to explain why.

When you try to make the distinction I believe I am reading, you are in essence stating that there is a qualitative and quantitative difference between interactions involving like and unlike polypeptides. In other words, in an A5 complex (5 subunits, all of type “A” polypeptide), the two sites on each “A” subunit needed to form the pentamer are in some way (as far as the concept of a “CCC” is concerned) fundamentally different from the interaction sites needed to make, say, an AB dimer. However, I am pretty sure you cannot call on any experimental or even theoretical study that tells us that two different sites on one polypeptide are conceptually different from one each on two different polypeptides. Worse still, Behe makes no such case in EoE. (Indeed, I believe he never anticipated this counterpoint; I also think, nay, relish the prospect that he will argue as you do rather than admit to his error.) Worse even more (for defenders of Behe), having examined (in the literature – I don’t do this work in my own lab) a number of interaction surfaces involving both homo-oligomers and hetero-oligomers, I can safely say that there is no conceptual difference between these possible class of interaction surfaces. I’m pretty sure anyone who studies these things would look at your argument and say “huh???”. It makes no sense, in fact it flies in the face of what we know about protein-protein interactions.

The bottom line – you (as well as other defenders of Behe – the idea isn’t new) are making claims about protein structure that are wrong. Your claims do not agree with anything we know, and seem to derive solely from a need to avoid the insult that the pentameric nature of Vpu does to Behe’s claims. This is not a very good reason to ignore all that is known about protein-protein interactions.

PaV said...

art said:

Once you finish this exercise, you will understand why Ian, and ERV, and Smokey, and everyone else here are accusing you of moving goalposts. The issue is protein binding sites, places where two different polypeptide chains (and they are different chains, even if they have the same sequence - if they were not different, there would only be one subunit) must interact. The fact that Vpu forms pentamers means that at least two "CCC"'s appeared from out of the blue.

I have several questions:

First, does vpu form said ‘ion-channels’ on the surface of CD4?
Answer: No.

Second, does vpu form said ‘ion-channels’ in the presence of a lipid bi-layer (membrane)?

Answer: Yes.

Third, is the ‘ion-channel’ that vpu form found in the virus itself?
Answer: No.

So, there is obviously some kind of biochemical effect that the lipid bi-layer has on vpu. The fact is that I’m being asked how many binding sites there are for the simple reason that the sequence space for such binding sites are so huge (involving only a single a.a. change, but spanning dozens of aa.’s in the meantime) that it is very hard to look at a sequence and to know where the binding is going to take place, and how it developed. So, I’m being asked because probably nobody really knows---or you would have pointed it out to me by now.

Now I ask the third question because if we look at the infamous Table 7.1 we find only one PTPBS listed: it’s for humans. Well, what is this PTPBS? It is, of course, the alpha-chain of hemoglobin becoming strongly attached to the beta-chain. Now, despite what ‘art’ says about there being ONE sequence, but two different ‘sub-units’, we don’t know any of this for a fact—unless someone would like to point it out in a very specific way. OTOH, we know that the alpha and beta chains of hemoglobin have ‘different’ sequences. And, not only that, if you look inside of a human, you’ll see that this PTPBS effects the human directly, whereas vpu’s ion channel capacity has only an indirect effect on the virus itself.

Next, let me point out a few things from “Edge of Evolution”:

First, on p. 124: “Proteins have complex shapes, and proteins must fit specifically with other proteins to make the molecular machinery of the cell.”

Second, on p. 125, we see Figure 7.1. What do we see? Two completely different proteins ‘fitting’ themselves together. In the legend underneath we read: “Both the shapes and the chemical properties of the protein surfaces must be complementary to bind.”

Third, as I’ve already pointed out, on p. 34: “In this book we are concerned with how machinery can be built. To build a complex machine many different pieces have to be brought together and fitted to one another.” (We, of course, see this in Figure 7.1)

Ian, in one post you talked about “reading for comprehension”. Well, isn’t it abundantly clear that what Behe is talking about, in a consistent way, throughout “Edge of Evolution” is the building up of complexity, the building up of molecular machinery in the cell? And that the mechanism for this build-up is the formation of PTPBS that give new functions? I think, to the objective reader, this is so.

Now, let me direct you again to Table 7.1. The one PTPBS we find there involves the interaction of two different chains of hemoglobin that now bind strongly together (so strongly, in fact, the their normal function is lost) that it doesn’t provide a haven for reproducing malarial cells, hence now providing a ‘new’ function: that of fending off malarial attacks.

To try and stretch ‘ion-channel’ formation through oligimerization of vpu to fit this category of Behe is, frankly, too big of a stretch, and represents, finally, the ‘moving of goalposts’.

__________________

Ian mentions that this ‘ion-channel’ has happened in historical times. That’s accurate enough. It came about, IIRC, in around the 30’s. (See here for Ian Musgrave’s phylogeny) That’s historic time. But, of course, this is Behe’s actual statement about HIV: p. 138 “The best current estimate is that a person infected with HIV is burdened with a total of one to ten billion (10^9 to 10^10) virus particles. The generation time for virus replication is about a day or two, so over the course of ten years a single person will produce more than a thousand generations of HIV, or up to 10^13 viruses. Since there are approximately fifty million people worldwide infected with the virus, the math points to a total of about 10^20 copies of the virus having been produced in the past several decades, when HIV became widespread in human populations—roughly the same as the number of malarial cells produced each year. . . .

“And exactly what has all that evolution of HIV wrought? Very little. . . . through all that, there has been no significant basic biochemical changes in the virus at all.”

(5 x 10^6) x (10^13)= 5 x 10^19, yearly rate. 10^20 develops in two years. But let’s take Behe’s several decades. So, going back to, what, the late 70’s, “there has been no significant basic biochemical changes in the virus at all.” So, why try and ‘sneak in’ something that happened in the 30’s while Behe is talking about ‘basic biochemical changes’ since the late 70’s? Your phylogeny even mentions that the receptor site change came about in the 60's. So what changes (let alone 'basic biochemical' changes) have come about since the late 70's?

Now, let me, gracious person that I am, concede your argument. Well, what happens?

Well, IDers would ‘have to admit’ that in the 10^20 replications of HIV-1, that, yes, indeed, ONE PTPBS developed. Maybe even TWO.

Behe mentions in his book that most cellular processes involve the interaction of 10 or more proteins. But, OK, we’ll concede the two. Now, by way of comparison, let’s calculated something; namely, how many ‘replications’ of elephants has there been since the time they first appeared in the fossil record? We’ll be generous in our assumptions. Let’s say that we assume the entire 65 million years that mammals have been around. Let’s say that there have been 100 million elephants world-wide who bear a baby elephant each year (the first number is high; the second is very high). What do we get?

(65 x 10^6 years) x (50 x 10^6 elephant-pairs worldwide each year) x (1 baby elephant/elephant pair)= 3.25 x 10^15 replications. That’s right! Not enough to even bring about one PTPBS!

________________

One final point. All of this has been, and is, a maddening exercise. Based on the calculation I just made, I think you should be taking a real long, hard look at what motivates you in all of this.

You’re “obsessed” with proving Behe wrong. This whole argument is because you want either a 1 or a 2 to be placed in his Table 7.1 for the HIV virus.

Well, let’s take another look at Table 7.1. We notice only 1 PTPBS, for humans. None for E. Coli, none for HIV, none for malarial cells. But did anyone pay attention to the numbers in the parenthesis? You’ll notice there that the 1 PTPBS that Behe mentions is for humans, and involves only 10^8 organisms. This 1 PTPBS/10^8 organisms is certainly better than 2 PTPBS/ 10^20 organisms.

So, you see, all of this is not really about science. It’s not about interpreting it correctly. It’s about “getting those IDers”. Yes, let’s “get” Behe to “admit” he was wrong about his comments, and Table 7.1 in particular. (Because then, of course, we can say, “Well, if he was ‘wrong’ about something so well-known, so simple as HIV, well, why should we, or anybody, take anything else he writes seriously.”)

Let me point this out to you. Notice that Behe has given you a ‘gift horse’ in Table 7.1. Now be off on your merry way.

Smokey said...

PaV wrote:
"First, does vpu form said ‘ion-channels’ on the surface of CD4 Answer: No."

Real answer: no, and this is a stupid question.

"Second, does vpu form said ‘ion-channels’ in the presence of a lipid bi-layer (membrane)? Answer: Yes."

Real answer: you don't have a clue. Not all lipid bilayers do the same thing as biological membranes. This is the converse of your equally idiotic false claim that the viral envelope is a protein, you see.

"Third, is the ‘ion-channel’ that vpu form found in the virus itself? Answer: No."

Real answer: you don't have a clue. Mechanisms for sorting viral proteins into virions are optimized for speed, not selectivity.

The problem is that each of your questions can be answered using data, but you, like Behe, are too intellectually lazy to look. Hint: the data won't be in the New York Times, where Behe stated under oath that he looks for data.

"So, there is obviously some kind of biochemical effect that the lipid bi-layer has on vpu."

Do you think that it floats around in the cytoplasm until it encounters a membrane, or are you about 40 years behind on your knowledge of basic molecular biology?

"The fact is that I’m being asked how many binding sites there are for the simple reason that the sequence space for such binding sites are so huge (involving only a single a.a. change, but spanning dozens of aa.’s in the meantime)..."

That's why Behe is FOS, PaV.

"... that it is very hard to look at a sequence and to know where the binding is going to take place, and how it developed."

People do experiments to figure those things out, and Behe stopped doing experiments about a decade ago. There's a good reason why.

"So, I’m being asked because probably nobody really knows---or you would have pointed it out to me by now."

Wow. What an incredibly stupid assumption.

"Now I ask the third question because if we look at the infamous Table 7.1 we find only one PTPBS listed:..."

What about all the ones that aren't listed? Are you really stupid enough to fall for Behe's lies of omission?

" it’s for humans. Well, what is this PTPBS? It is, of course, the alpha-chain of hemoglobin becoming strongly attached to the beta-chain."

PaV, assuming you're a human, how long does it take YOU to evolve a new protein with a highly specific binding site?

"Now, despite what ‘art’ says about there being ONE sequence, but two different ‘sub-units’, we don’t know any of this for a fact—unless someone would like to point it out in a very specific way. "

Art already did--you're just not bright enough to understand it.

"Next, let me point out a few things from “Edge of Evolution”:..."

No, you need to see if Behe's claims from EoE match the data. They don't.

"First, on p. 124: “Proteins have complex shapes, and proteins must fit specifically with other proteins to make the molecular machinery of the cell.”"

Wrong. Selectivity is all that is required. If you don't understand the difference, figure it out before posting more idiocy like this.

"... Well, isn’t it abundantly clear that what Behe is talking about, in a consistent way, throughout “Edge of Evolution” is the building up of complexity, the building up of molecular machinery in the cell? And that the mechanism for this build-up is the formation of PTPBS that give new functions? I think, to the objective reader, this is so."

No, because as Ian pointed out, your goalpost move eliminates the eubacterial flagellum.

"Now, let me direct you again to Table 7.1. The one PTPBS we find there..."

But what about all the ones we find in nature?

"(65 x 10^6 years) x (50 x 10^6 elephant-pairs worldwide each year) x (1 baby elephant/elephant pair)= 3.25 x 10^15 replications. That’s right! Not enough to even bring about one PTPBS!"

Then, as I love to point out, you've got a testable hypothesis (you will not find a single new PTPBS in elephant biochemistry) that my hypothesis (that you are fundamentally dishonest) predicts that you will not lift a finger to test.

Just like Behe, you're a fraud.

PaV said...

For the third time, Smokey, please don't respond to my posts. I refuse to respond to you.

ERV said...

Smokey is allowed to post just like youre free to ignore him.

I dont ban people.

Ill get a response to you tomorrow, PaV-- alas, today was laundry day, clean the apartment day, grocery shopping day, and Big Run day, so Im going to sleep in like 30 minutes :P

But thank you for your posts, as Ive been learning a lot from them, and the responses.

Hermagoras said...

The way I see it, the differences between PaV's and the standard approach don't boil down either to lying or stupidity. It's rather a question of a kind of specialized working literacy characteristic of science (and of other highly skilled professions too). From what I can tell, most working biologists who have responded to Behe's work have dismissed it. ERV found that his account of HIV didn't square remotely with what she knew to be the case, and has tried to explain this here. Yet a lot of people -- not working biologists, from what I can tell -- have taken Behe's arguments seriously.

Let me give an analogy. For about ten years, I taught college writing courses in the prison system in my state. A number of prisoners would read law texts in the prison library and make written arguments for why their convictions should be overturned based on what they read in the statutes. Most of these people had no attorneys, having already been convicted. So they'd submit their own motions. The motions looked reasonable to them, based on their prison-library understanding of the law. But they'd never fly in the courtroom, because they didn't possess the day-to-day working literacy of the practicing attorney. I think the success of Behe in particular, and ID in general, among some laypeople comes from the lack of working literacy of biology among the general public.

Smokey said...

"For the third time, Smokey, please don't respond to my posts. I refuse to respond to you."

Shove your mendacity up your ass, PaV.

Hermagoras, your analogy is faulty, because the prisoners at least made an effort to understand the law, while PaV is lying and pretending that he can't do sequence alignments on the Web.

IMO, if you make no attempt to examine evidence and implicitly claim familiarity with it, as PaV did when he answered his stupid questions with assumptions instead of data, you are lying. Your intent is to deceive your audience into thinking that you are familiar with the evidence.

Hermagoras said...

Smokey,

You may be right. Certainly my prisoner students had a stake in getting the lawa right, however much they screwed it up

H

Hermagoras said...

correction: for "lawa" read "law."

Ian Musgrave said...

PaV wrote:
So, there is obviously some kind of biochemical effect that the lipid bi-layer has on vpu.


Look, PaV, it’s obvious you know little about biology or biochemistry. I’m currently infected with influenza A H1N1, and I’m not really up to the detailed biology 101 you need to get all this, but bear with me as I try and explain this.

Cell membranes, such as the membranes of red blood cells, liver cells, and CD4+ lymphocytes, are all lipid bilayers, with proteins embedded in them. The CD4+ subclass of lymphocytes have a particular protein, CD4 in their membrane. CD4 is a transmembrane domain protein, in that the protein passes through the membrane and has an extracellular and intracellular domain. Vpu is also a transmembrane domain protein, part of it passes through the membrane. In SIV, HIV-1-O and HOV-1-N it passes through the membranes, and remains a monomer. Only in HIV-1-M does it form a viroporin. It is not the membrane doing it, but the changes in structure of the Vpu protein that allows it to bind to itself to become a pentamer with a central hole that makes it an ion channel (except to the extent you need a membrane for there to be an inside and outside to a cell for ions to pass into). To ask if ion channels form on the surface of CD4 is meaningless, it is a single protein that doesn’t have an “in” or “outside”. Vpu does bind to CD4; in SIV, HIV-1-O and HIV-1-N VPU links CD4 to the SCF ubiquitin ligase and facilitates the entry of CD4 into the protein degradation pathway. In HIV-1-M Vpu binds CD4 but also targets the Gogli apparatus, making binding and degradation of CD4 far more efficient. As well, Vpu now forms a pentamer which is an ion channels, which enhances the release of viral particles. CD4 can be bound to the pentamer, but it is meaningless to ask if it forms an ion-channel in its surface (no ion channel can form “in” CD4).

Pav wrote: if we look at the infamous Table 7.1 we find only one PTPBS listed: it’s for humans. Well, what is this PTPBS? It is, of course, the alpha-chain of hemoglobin becoming strongly attached to the beta-chain. .

Once again, Behe gets this story dead wrong. The alpha-beta interaction didn’t evolve in humans, but way back from homodimer binding sites. In some of the simplest vertebrates, hagfish, haemoglobin is a monomer which can associate into a homodimer. In later vertebrates such as the shark the haemobglobin gene got duplicated, and the two duplicates diverged into alpha and beta chains, but they still used the original globin-globin binding sites that formed the homodimers. Some extra binding sites developed in bony fish, but the alpha–beta binding sites were the globin-globin binding sites (no binding sites of any importance developed in humans, or mammals really, the sickle cell anemia mutation is a one amino acid change which is not doing anything novel mechanistically). Thus Behe’s example sinks your contention. (For more things that Behe gets wrong about haemoglobin, see this post )

The one PTPBS we find there involves the interaction of two different chains of hemoglobin that now bind strongly together

That’s a plain silly example. A single amino acid mutation that makes haemoglobin bind more tightly (all it does is alter an existing binding point, not create a new one), vs a multiple amino acid change that produces a new structure, with a function not found in the original monomeric protein, that aids the virus to replicate more efficiently. If you cannot see how forming a new structure with a new function trumps “binding more tightly”, then you need to seriously rethink your understanding of biology.

Since there are approximately fifty million people worldwide infected with the virus, the math points to a total of about 10^20 copies of the virus having been produced in the past several decades, when HIV became widespread in human populations

Except Vpu gaining viroporin activity and Golgi apparatus targeting occurred in roughly 10 years, when the infections were just starting, and the total populations infeceted were in the thousands. So, two new binding sites (Vpu viroproin and Golgi targeting) in less than 10 years in a few thousand people. So far fewer than 10^20 viruses were involved, possibly somewhere between 10^13 or 10^14 as the replication rate of the pre HIV-1-M viruses is lower that the post Vpu-ion channel viruses. Behe’s figures don’t look so impressive now.

Well, IDers would ‘have to admit’ that in the 10^20 replications of HIV-1, that, yes, indeed, ONE PTPBS developed. Maybe even TWO.

No, two new binding sites (Vpu viroproin and Golgi targeting) in far, far less that 10^20, a third (the plasma membrane site) arose in the 60’s, when the infected population was still rather small, still far less than 10^20. If the second HIV-1-M-C sequence turns out to be a gating sequence, that’s 4. And that is just Vpu. We haven’t discussed the viruses which have switched from CD4 binding to binding cytokine receptors for example.

Look, PaV, let’s face it, Behe is dead wrong about this. You really need to be more informed about biology, but even with your knowledge you should be able to see that Behe has messed up badly here (not to mention he gets his figures from flawed guestimate about how often malaria arose, and some of his required malaria mutations are not). Now think carefully about this, Behe couldn’t even get the HIV binding site story right, something that a fairly simple PubMed search would show up (or the required malaria mutations right), what else is he wrong about?

Think it over, I’m off to bed with my influenza infection.

Ian Musgrave said...

PaV wrote: So, there is obviously some kind of biochemical effect that the lipid bi-layer has on vpu.

Note that this argument also applies to the bacterial flagellum (it's baically an oligomer of FlgG punching a hole through the bacterial membrane)

art said...

PaV, your questions or points for me are getting a bit muddled. But you make one comment that demands correction:

Now, despite what ‘art’ says about there being ONE sequence, but two different ‘sub-units’, we don’t know any of this for a fact—unless someone would like to point it out in a very specific way.

No, we know it absolutely for a fact.
-------------------
Virol J. 2007 Aug 29;4(1):81 [Epub ahead of print]

Oligomerization of the human immunodeficiency virus type 1 (HIV-1) Vpu protein - a genetic, biochemical and biophysical analysis.

Hussain A, Das SR, Tanwar C, Jameel S.

ABSTRACT: BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) is a
complex retrovirus and the causative agent of acquired immunodeficiency syndrome (AIDS). The HIV-1 Vpu protein is an oligomeric integral membrane protein essential for particle release, viral load and CD4 degradation. In silico models show Vpu to form pentamers with an ion channel activity. RESULTS: Using Vpu proteins from a primary subtype C and the pNL4-3 subtype B isolates of HIV-1, we show oligomerization of the full-length protein as well as its transmembrane (TM) domain by genetic, biochemical and biophysical methods. We also provide direct evidence of the presence of Vpu pentamers in a stable equilibrium with its monomers in vitro. This was also true for the TM domain of Vpu. Confocal microscopy localized Vpu to the endoplasmic reticulum and Golgi regions of the cell, as well as to post-Golgi vesicles. In fluorescence resonance energy transfer (FRET) experiments in live cells we show that Vpu oligomerizes in what appears to be either the Golgi region or intracellular vesicles, but not in the ER. CONCLUSION: We provide here direct evidence that the TM domain, is critical for Vpu oligomerization and the most favourable channel assembly is a pentamer. The Vpu oligomerization appears to be either the Golgi region or intracellular vesicles, but not in the ER.
-------------------------

One more thing, PaV - you seem to be avoiding the simple question I asked - how can one get a pentamer formed by five "like" subunits? What is the minimum number of protein interaction sites you need? We don't need to make any assumptions about the numbers of amino acids involved - we can just count the hypothetical contacts. Given that we know for a fact that vpu forms a pentamer, it would be nice of you to answer my question. It doesn't take a long answer, and you don't need to be a rocket scientist (or a crystallographer) to figure it out.

Smokey said...

Will PaV:

1) concede all of these points, or
2) pretend that his theses haven't been ripped to shreds, but still come up with a new, even more bogus, argument without evidence?

Ian Musgrave said...

One issue with Behe's confident pronouncement that humans have only one new binding site developing in historic times is that when it comes to humans, we really only notice disease genes, and even then when they are really, really obvious. Modest changes in gene products that have subtle effects on health will be missed.

One that wasn't missed was the Apolipioprotein AI-M mutation. This is a mutation that strengthens the binding between Apo AI monomers to form dimers more easily, and gives Apo AI-M an antioxidant role. As a result, it lowers heart attcak risk in the population that bears it.

So if Behe counts the HbS mutation, why doesn't he count the Apo AI-M mutation? (and how many more has he missed?)

PaV said...

art:

You quote me as follows:

"Now, despite what ‘art’ says about there being ONE sequence, but two different ‘sub-units’, we don’t know any of this for a fact . . . "

Based on the article you posted, my guess is that the both of us have two different definitions of what "sub-units" mean. Frankly, I wasn't quite sure what you meant. Based on the context, I was assuming you meant that two different kinds of structural folds had been introduced into the sides of the oligomerized vpu protein. But I hadn't seen anything suggesting such detailed structural knowledge, and so it seemed to be just a hypothesis. It would now appear that by "sub-units," you mean the monomer form and the viroporing (pentamer) form. Is that correct?

I've had two long, hard days, with no time to post. (I'm too tired to think straight) Tomorrow I'm gone for most of the day again. So, I'll catch up with things likely on Wednesday.

Ciao!

P.S. Ian, I hope you're feeling better.

Chris Noble said...

Pav, who are you trying to convince?

Has it ever occurred to you that just perhaps you might not have a clue what you are talking about?

I admire your courage in debating a topic in which you are clueless and your opponents are knowledgable but courage and conviction are no substitute for knowledge.

Smokey said...

PaV wrote:
"It would now appear that by "sub-units," you mean the monomer form and the viroporing (pentamer) form. Is that correct?"

That's not what "subunit" means, and it doesn't have a hyphen.

"I've had two long, hard days, with no time to post. (I'm too tired to think straight)"

I don't think that fatigue is the problem.

Torbjörn Larsson said...
This comment has been removed by the author.
Torbjörn Larsson said...

So if Behe counts the HbS mutation, why doesn't he count the Apo AI-M mutation?

Let me see if I understand this.

First, the factual errors:

- Behe has made an "infamous table" where he lists a new protein-protein binding site for humans at a much higher evolution rate than he considers possible. That is a poo poo to add to the growing heap.

- Behe mistakenly lists as a protein-protein binding site evolution a hemoglobin trait that was developed in fish instead of humans. Another poo poo to my list.

- Behe doesn't list a gene duplication (and subsequent divergence) which results in a new protein-protein binding site added to our hemoglobin. Another poo poo.

- Behe doesn't list a new protein-protein binding site that actually evolved in humans. Poo poo.

Second, the logical errors:

We observe evolution to happen, so the creationist probability argument is superfluous.

But if we humor it and Behe's numbers, we see that in mammals we can have a proxy for evolution rate of 1 protein-protein binding site in 10^8 human individuals. At the same time we observe a number of new protein-protein binding sites in at most 10^14 HIV individuals.

The difference would have some obvious causes:
- HIV genome are extremely space constrained due to the transmission mechanism.
- Retrovirus can presumably pick up genes from hosts, but due to the space constraint their genome transcription is severely constrained.
- Humans sexuality gives higher evolution rates than for asexual populations.

I think that adds up to those numbers being reasonable so far, in spite of one of them being provided by Behe. So Behe's 10^20 is really on the order of 10^8.

Another factual poo poo, adding up to 5 new creationist-error binding sites, for a grand total of 10 on my list of EoE factual errors. Also, I must note that being wrong with 12 orders of magnitude is only beginning to describe how wrong creationist dogma is.

PaV said...

“PaV: So, there is obviously some kind of biochemical effect that the lipid bi-layer has on vpu.”

Ian: “Look, PaV, it’s obvious you know little about biology or biochemistry. . . . Cell membranes, such as the membranes of red blood cells, liver cells, and CD4+ lymphocytes, are all lipid bilayers, with proteins embedded in them.”

Ian, if you look at what I posted, I had the word “membrane” in parenthesis. I full-well know that membranes are more or less ‘lipid by-layers’. Why did you leave that word in parenthesis out when you quoted me? I’m curious.


Ian wrote: “I’m currently infected with influenza A H1N1, and I’m not really up to the detailed biology 101 you need to get all this, but bear with me as I try and explain this.”

No need to give me detailed biology 101 information (as if biology 101 was that detailed), I have a degree in biology. I’ve also taken a course in biochemistry. I’ll date myself: we used one of the first editions of Lehninger.

IM: The CD4+ subclass of lymphocytes have a particular protein, CD4 in their membrane. CD4 is a transmembrane domain protein, in that the protein passes through the membrane and has an extracellular and intracellular domain.”

Ian, I believe you just mixed up CD8 with CD4. CD4 attaches to the membrane while its immunoglobulin ends are outside of the T-cell. (See here) CD8 appears to be a transmembrane domain protein, however.



IM: ”Vpu is also a transmembrane domain protein, part of it passes through the membrane. In SIV, HIV-1-O and HOV-1-N it passes through the membranes, and remains a monomer.” Only in HIV-1-M does it form a viroporin. It is not the membrane doing it, but the changes in structure of the Vpu protein that allows it to bind to itself to become a pentamer with a central hole that makes it an ion channel (except to the extent you need a membrane for there to be an inside and outside to a cell for ions to pass into).”

In a 2003 review article (here), the “transdomain” portion of vpu appears at the very beginning of the N-terminal end, which suggests that there’s nothing left to pass all the way into the interior of the cell. In this same review article, it suggests that the likely orientation of vpu is the pentamer; but this is something arrived at through some kind of computer modeling and they don’t discount the possibility of it being a tetramer. But this is a minor point, really, as far as your argument goes. You say, rightly, “Only in HIV-1-M does it form a viroporin. It is not the membrane doing it, but the changes in structure of the Vpu protein that allows it to bind to itself to become a pentamer with a central hole that makes it an ion channel (except to the extent you need a membrane for there to be an inside and outside to a cell for ions to pass into).” This indicates that you understood the argument I was making in the previous post, distinguishing from vpu in its purified state (IOW, it doesn’t oligomerize all by itself outside of the membrane—for that would be very problematic in other ways, a point I was making) and that in the viroporin configuration. And, yes, indeed, some changes in vpu must have taken place or else you wouldn’t have the various classes of HIV. Nevertheless, (and ‘art’, this is an answer to your question) no one really knows ‘how many changes’ and ‘what kind of changes’ took place for the viroporin to form. (Incidentally, in the review article they make it clear that, at least in 2003, there was some suspicion that vpu viroporing didn’t form an ‘ion-channel’, but, rather a “physical pore”—hence the name “viroporin”.

So, what has changed in vpu? How many changes have come about? Art was asking me how many points of interaction were needed to form a pentamer of vpu protein. Well, it all depends, doesn’t it? If vpu formed an ‘oligomer’ in solution, then I would think there would have to be quite a number of interactions between the various a.a.’s of the protein. (Btw, I think it healthy to distinguish between chemical interactions and ‘binding sites’ per se, since in a very recent article, posted on UD, they’ve found a very ‘dynamic’ kind of em/quantum effect between series of amino acids which gives rise to the ‘binding’ attraction) But, when the oligomerization takes place in a membrane, then you have the membrane itself helping to hold the pentamer together. Now, as I’ve previously posted, a simple serine insertion into a small string of base a.a.’s was sufficient to replace a ckII (IIRC) binding site; so is one a.a. just in the right place enough? Is two? There are only about 28 or 29 aa’s involved in the TM of vpu; but, if you compare vpu with M2, which I'll do at the end of this post, you'll find they share a TM string of only 18 or 19 aa, and M2 is your prototypical viroporin, so one or two, just in the right place, could have a considerable effect.

But, we’re left to guessing, aren’t we? Yes, computer modeling can be done, and effects simulated, but that only gives us a statistically accurate picture of what’s going on. Art, maybe you have some information from some of these kinds of simulations you’d like to share. But, my guess would be one or two a.a. substitutions would be sufficient to change from monomer to pentamer (?)

One last thing, the review article indicates that upwards of 97% of vpu is found elsewhere than the cell membrane, mostly the ER and Golgi body.


To ask if ion channels form on the surface of CD4 is meaningless, it is a single protein that doesn’t have an “in” or “outside”. Vpu does bind to CD4; in SIV, HIV-1-O and HIV-1-N VPU links CD4 to the SCF ubiquitin ligase and facilitates the entry of CD4 into the protein degradation pathway.

Admittedly, I didn’t phrase the question well. But the point I was making was that vpu doesn’t ‘oligomerize’ all on its own. And, yes, CD4 is a protein. But, as I pointed out before, it is not a transmembrane protein like vpu (which is a type I transmembrane protein). But the C-terminal end of vpu, not the N-terminal end, is what is likely involved in its interaction with CD4, possibly causing the CD4 to lose its anchoring in the cell membrane, and faciliatating its binding with the SCF ubiquitin ligase. But this does point out the multi-functionality of vpu.

IM:
Pav wrote: if we look at the infamous Table 7.1 we find only one PTPBS listed: it’s for humans. Well, what is this PTPBS? It is, of course, the alpha-chain of hemoglobin becoming strongly attached to the beta-chain.”

Once again, Behe gets this story dead wrong. The alpha-beta interaction didn’t evolve in humans, but way back from homodimer binding sites. In some of the simplest vertebrates, hagfish, haemoglobin is a monomer which can associate into a homodimer. In later vertebrates such as the shark the haemobglobin gene got duplicated, and the two duplicates diverged into alpha and beta chains, but they still used the original globin-globin binding sites that formed the homodimers. Some extra binding sites developed in bony fish, but the alpha–beta binding sites were the globin-globin binding sites (no binding sites of any importance developed in humans, or mammals really, the sickle cell anemia mutation is a one amino acid change which is not doing anything novel mechanistically). Thus Behe’s example sinks your contention.

This is all very nice information; however, it misses the point entirely, and, thusly, does not sink my contention.

Whatever the “evolution” of the alpha-to-beta binding, this binding has “changed”. The alpha chain is now binding so strongly to the beta chain as to cause their agglomerization. This sets up a whole string of physiological changes which (1) cause enormous pain to those with sickle-cell, and (2) can prove fatal.

So, while it’s possible that the “binding sites” might be the same, the “binding energy” has certainly increased. And, again, why do you fight to prove that Behe is wrong about zero PTPBS when it comes to the mutational powerhouse that HIV is, and then turn around and fight to prove that he’s wrong to say that humans have come up with a PTPBS in such few replications when we aren’t mutational powerhouses? Are you “cutting off your nose to spite your face”?


IM: “A single amino acid mutation that makes haemoglobin bind more tightly (all it does is alter an existing binding point, not create a new one), vs a multiple amino acid change that produces a new structure, with a function not found in the original monomeric protein, that aids the virus to replicate more efficiently. If you cannot see how forming a new structure with a new function trumps “binding more tightly”, then you need to seriously rethink your understanding of biology.”

Is it a “multiple amino acid change”? Have the computers shown it to be so?
Ian, what you keep failing to acknowledge is that Behe is clearly intent on protein interactions that involve dissimilar proteins. Technically, and only technically, is a viroporin vpu a PTPBS. But only in a trivial way. Alpha-chains of heamoglobin “bind” with beta-chains of hemoglobin in sickle-cell patients. They “bind” together out of solution. vpu doesn’t do that. Why can’t you see the significant difference between these two separate events. If you want to say that Behe hasn’t defined a PTPBS properly, fine, make the argument. But, according to what Behe has defined, vpu wouldn’t fall into this category while even what you consider to be a small change between alpha and beta chains does.

IM:
PaV: Since there are approximately fifty million people worldwide infected with the virus, the math points to a total of about 10^20 copies of the virus having been produced in the past several decades, when HIV became widespread in human populations

“Except Vpu gaining viroporin activity and Golgi apparatus targeting occurred in roughly 10 years, when the infections were just starting, and the total populations infeceted were in the thousands. So, two new binding sites (Vpu viroproin and Golgi targeting) in less than 10 years in a few thousand people. So far fewer than 10^20 viruses were involved, possibly somewhere between 10^13 or 10^14 as the replication rate of the pre HIV-1-M viruses is lower that the post Vpu-ion channel viruses. Behe’s figures don’t look so impressive now.”

This opens up another can of worms, one I don’t care to delve in since my point has been made; namely, that Behe calculated that in the last few decades 10^20 HIV viruses have duplicated WITHOUT any NOVEL biochemical changes. You don’t dispute that. You simply want to move the argument to a time frame that falls outside of what Behe says in EoE. Nonetheless, what Behe writes is factually correct. You can’t dispute that. All you can do is to say that what Behe has in Table 7.1 is ‘misleading’.

So, let’s look at the facts. In 10^20 replications, HIV, over the last two or three decades, has shown no signs of any biochemical novelty. What it did prior to 1977 is one thing, but we have seen that it is possible for HIV to replicate 10^20 times without a single biochemical change.

As I pointed out in my last post, “how many ‘replications’ of elephants has there been since the time they first appeared in the fossil record?” Since the time that elephants first appeared in the fossil record, a most generous calculation shows “(65 x 10^6 years) x (50 x 10^6 elephant-pairs worldwide each year) x (1 baby elephant/elephant pair)= 3.25 x 10^15 replications.” Not even enough for one CCC!


IM:
PaV: “Well, IDers would ‘have to admit’ that in the 10^20 replications of HIV-1, that, yes, indeed, ONE PTPBS developed. Maybe even TWO.”

IM: No, two new binding sites (Vpu viroproin and Golgi targeting) in far, far less that 10^20, a third (the plasma membrane site) arose in the 60’s, when the infected population was still rather small, still far less than 10^20. If the second HIV-1-M-C sequence turns out to be a gating sequence, that’s 4. And that is just Vpu. We haven’t discussed the viruses which have switched from CD4 binding to binding cytokine receptors for example.

How do you know that viroporin and Golgi targeting are separate events? As the review points out, almost 97% of vpu is in the ER and Golgi body.

But all of this is no more than picayune nonsense. First, what else do we find in Table 7.1? Behe notes this: “PROTEIN-BINDING SITES FOUND IN A TYPICAL CELL: 10,000”. 10,000 binding sites!! And I’m supposed to be impressed with two, or three, or four binding sites? And in how many replications? You very coyly state: “in less than 10^20 replications”. The fact is is that one single person infected with HIV can replicate and produce by themselves 10^9 to 10^10 viruses a day (And this is conservative. The likely numbers are 10^10 to 10^12/day) Replication time is 1.5 days. So, if a thousand people had HIV in the 60’s, in five years time we have: 10^10viruses/replication cycle x 200 replication cycles/yr. x 5 yrs. x 1000 people= 10^16 viruses. And how many elephants ( in a most generous calculation) have EVER lived since the time of the first mammals 65 million years ago? 3.25 x 10^15. That’s one-third the number of HIV replications. So, if HIV developed three PTPBS in those 5 years (which, of course, they didn’t), then that means we should expect “one” novel PTPBS arising in those 65 million years of elephant existence. Is this somehow impressive? Am I to think how wonderful, how powerful RM+NS is? Well, obviously, I don’t.

IM: “Look, PaV, let’s face it, Behe is dead wrong about this. You really need to be more informed about biology, but even with your knowledge you should be able to see that Behe has messed up badly here (not to mention he gets his figures from flawed guestimate about how often malaria arose, and some of his required malaria mutations are not). Now think carefully about this, Behe couldn’t even get the HIV binding site story right, something that a fairly simple PubMed search would show up (or the required malaria mutations right), what else is he wrong about?”

Behe’s figures are correct. You’ve tacitly admitted it. As far as I’m concerned, this argument is finished.

You simply care to indulge in picayune arguments that amount to “straining gnats, and swallowing elephants.” My sense is that you haven’t read Behe’s book. That’s your prerogative. But if you’re going to attack him over picayune matters, then read the book; find out what he actually says.

Here’s an extended quote that makes my point:

“Could the edge of evolution be as close as a single cellular protein-to-protein binding site, rather than two? After all, no new such interactions have been uncovered in malaria and HIV. Could it be that shape-space reasoning has significantly underestimated the difficulty of developing a single new binding site in the crowded tightly regulated interior of a cell? That’s possible, and we always have to keep in mind that these estimates are rough and will be revised as more information becomes available. Still, I think its better to err on the side of caution, allow room for the odd exception like sickle hemoglobin, and draw the line at complexes of three kinds of proteins (that is, two binding sites), as I do in Figure 7.4.”

Notice he says “kinds”. vpu binding to itself is not two “kinds”, it’s one “kind”. Notice he says “three kinds of protein (that is, two binding sites)”. Obviously he means protein A develops a new binding site in conjunction with protein B, and together with A and B, protein C forms a binding site with the AB complex. So, in what way, then does vpu forming a binding site with casein kinase, or with CD4, or with itself, or with the Golgi body, involve more than two “kinds” of proteins? IOW, Behe is willing to “concede” more than you can “demonstrate.”

Just in passing, I was most intrigued by the review article by Maria Eugenia Gonzalez and Luis Carrasco. In that paper they indicate the TM domains of M2 and vpu. It turns out that there’s more of a match between M2 and vpu than vpu and any other viroporin forming virus. Not only that, here’s how the sequences line up:

vpu: MQPIQIAVALVVAIIIAIVVWSIVII

M2: PLVVAASIIGILHLILWIL

The bold face a.a. match up. For M2, 8 out of 19 a.a. line up with the vpu sequence. That’s 42% similarity. Here’s what you said Ian: “In terms of sequence, there is no significant sequence similarity between M2 and Vpu (sequences and alignments on request).” And here’s what ERV wrote: “The amino acid similarity between HIV-1 Subtype B Vpu and SIVcpz Vpu is ~37%.”

So, let’s see. You say M2 and vpu have no significant similarity, while I show, based on a review article, 42% similarity, which is even more than when HIV-1 Subtype B vpu is compared to itself in SIVcpz. No significant similarity? I’m no flu expert, but didn’t type A influenza go crazy in the 1910’s and 20’s? And didn’t “ion-channel” activity show up in HIV around that time?

Finally, somewhere in my reading, I thought I read that we don’t find simian flu’s because they have some kind of molecule in their membrane that prevents ion-channels from developing. Maybe that’s why we don’t see vpu in the simian lines. I can’t find the reference, though I looked and looked. But if, indeed, simians have some molecule in their membranes that prevent ion-channel flow, it would drastically reduce the virulence of HIV-1 if that molecule were isolated and therapeutically given to HIV sufferers. Doesn’t some enterprising grad student want to take a preliminary look into all of this?

PaV said...

Chris Noble said:

"Has it ever occurred to you that just perhaps you might not have a clue what you are talking about?"

Has it ever occurred to you that Ian doesn't know what he's talking about?

This isn't a matter so much of HIV expertise, of which I imagine Ian has lots of. It's about following the argument that Behe makes in EoE, and then critiquing it in a meaningful way. What Ian was doing, whether intentionally or not, was to conflate the biochemcial history of HIV-1, which spans almost 80 years, into about a 10-year span in the sixties (when HIV was less prevalent, and when two notable changes occurred to HIV). That's not being fair to Behe's assessment of HIV, which covers the time since the late 70's to the present.

I'm surprised that you aren't shocked by the fact that I calculated 10^15 elephants in the entire history of animal life, and yet, in 10^20 replications (HIV progeny) of HIV, nothing has happened in the last twenty, thirty years. What does that say about the limits of RM+NS? Behe states that 10,000 protein-to-protein binding sites are needed in the cell, and yet, in the last twenty or thirty years, in 10^20 replications of HIV-1, nothing has happened; in 10
^20 replications of malaria (a eukaryote), no ptpbs has developed. These are huge, order of magnitude differences between what nature requires and what RM+NS can produce. Doesn't that concern you?

Chris Noble said...

This isn't a matter so much of HIV expertise, of which I imagine Ian has lots of. It's about following the argument that Behe makes in EoE, and then critiquing it in a meaningful way.

No, you are simply trying to avoid admitting that Behe was wrong.

There is no meaningful distinction between 5 Vpus binding together and two different proteins binding together. This is just an ad hoc excuse.

Your idea about influenza M2 and HIV-1 Vpu is another ad hoc excuse.

If Behe had balls and really believed in an "edge of evolution" then he should point to something that is beyond the edge. At what point did the "Designer" step in and shuffle a few base pairs? The mutations that allowed SIV to infect humans?

PaV said...

Ian said:

"One that wasn't missed was the Apolipioprotein AI-M mutation. This is a mutation that strengthens the binding between Apo AI monomers to form dimers more easily, and gives Apo AI-M an antioxidant role. As a result, it lowers heart attcak risk in the population that bears it.

So if Behe counts the HbS mutation, why doesn't he count the Apo AI-M mutation?"


I can only guess that you haven't really read Behe's book. Maybe you don't want to stoop so low as to read anything he wrote. I don't know. But the reason why Behe wouldn't include this kind of mutation in his book is quite obvious to anyone who has read the book. He's chosen for his anaylsis something that has been scientifically well-documented over the last forty or fifty years; namely, malaria, sickle-cell anemia, and developed drug resistance in malaria. His numbers in Table 7.1 reflect the "trench warfare" that has taken place between humans and P. falciparum over recent times. So, that's why Apolipioprotein AI-M is of no concern to him. Does anyone have any idea whatsoever how this mutation originated, or when, to whom is was passed on, and the length of time that it has been in the part of Italy where it was found? Where would Behe get numbers for the 'number of replications'?

Chris Noble said...

I'm surprised that you aren't shocked by the fact that I calculated 10^15 elephants in the entire history of animal life, and yet, in 10^20 replications (HIV progeny) of HIV, nothing has happened in the last twenty, thirty years. What does that say about the limits of RM+NS?

It says a lot about your understanding of evolution. The current strains of HIV have continued to spread throughout the world. What do you think HIV should have done? Grown wings?

What are the selective pressures on HIV? HIV shows rapid evolution of the env gene. Drug resistant mutants pop up. This is hardly nothing.

What exactly should HIV have done?

PaV said...

Chris Noble said:

No, you are simply trying to avoid admitting that Behe was wrong.

When it is pointed out to me that Behe is wrong, I will accept that. Ian made a mistake confusing CD4 and CD8, does that invalidate everything else he's written? I don't think so. But why this need for a "gotcha" moment? There's absolutely no perspective in all of this.

There is no meaningful distinction between 5 Vpus binding together and two different proteins binding together. This is just an ad hoc excuse.

One shouldn't equate a 'simple' chemical bond with what happens in a 'binding site'. I've already alluded to a recent paper that indicates this. That said, having 5 vpu's bind together, while involving certain a.a. changes, is not the stepping stone to life. Remember that viruses aren't considered life. You have to have protein complexes form before you can have life as we know it. Therefore, Behe thinks in terms of PTPBS between "kinds" of proteins.

Finally, oligomerization of vpu took place in the 30's. Behe's focus is the late 70's and later. On what basis can you critique what Behe says about HIV in the latter part of the twentieth century with what happened in HIV in the early part?

In the end, Behe concedes more than Ian has demonstrated. So why the harangue?


Your idea about influenza M2 and HIV-1 Vpu is another ad hoc excuse.

Actually it was meant as an ad hoc conjecture. Since I've posted it, I've thought it over, and it would only make sense that those parts of proteins that have the same function will likely have the same overall structure as well, and, hence, similar sequencing. But, outside of those regions, they can be very dissimilar. And, outside of the TM region M2 and vpu are so dissimilar that I think it would be better to just think of their similarity in the TM as a bit of homology.

If Behe had balls and really believed in an "edge of evolution" then he should point to something that is beyond the edge. At what point did the "Designer" step in and shuffle a few base pairs? The mutations that allowed SIV to infect humans?

You appear to have become frustrated and desperate.

Chris Noble said...

The bold face a.a. match up. For M2, 8 out of 19 a.a. line up with the vpu sequence. That’s 42% similarity.

Ummm, but inluenza A M2 and HIV-1 Vpu are 97 and 81 AAs in length.

If you want to do the alignment properly:

vpu: LVVA

M2: LVVA

Wow! 4 out of 4! 100% similarity!

PaV said...

Chris Noble said:

"The current strains of HIV have continued to spread throughout the world. What do you think HIV should have done? Grown wings?"

Exactly. That's the whole point here. Elephants have produced 10^15 offspring in 65 billion years. HIV produces that many offspring in a modest two year period. How many offspring of HIV will it take before we see ONE new gene in it? It has what, 9 genes. Well, Uncle Ben's Converted Rice has 56,000 genes. As I said before, it's an order of magnitude problem here.


What are the selective pressures on HIV? HIV shows rapid evolution of the env gene. Drug resistant mutants pop up. This is hardly nothing.

Behe, again, concedes as much. He tells the reader that drug resistance in bacteria is an example of RM+NS. This is "conceded". But what else can it do? When Behe tries to look into that, his answer is: "very little."


What exactly should HIV have done?

Grown a beard!

PaV said...

Chris Noble said:

"Ummm, but inluenza A M2 and HIV-1 Vpu are 97 and 81 AAs in length."

Remember I was citing a paper. In that paper they identified the hydrophobic, transmembrane portions of both proteins. On that basis, I said the similarity was 8 out of 19, or 42%. But, afterwards--don't get old because small type throws you even with bi-focals!--I saw that it was 7 out of 19, or 37%.

So thanks for giving me the opportunity for correcting the mistake. And, again, I've posted that we're just seeing a homology of sequencing that matches a homology in function, and no more. M2 and vpu are very dissimilar outside this one region. Now, if it's possible for just that one portion of sequencing to be captured by HIV, that's a different matter; but, as I said in response to you already, it was no more than an ad hoc conjecture in the first place.

Chris Noble said...

When it is pointed out to me that Behe is wrong, I will accept that.

Your refusal to admit that Behe is wrong has little to do with reality. The only thing that you have demonstrated is your willingness to in vent ad hoc excuses and engage in silly rhetorical words games where Behe's words are reinterpreted to avoid dealing with factual errors.

One shouldn't equate a 'simple' chemical bond with what happens in a 'binding site'. I've already alluded to a recent paper that indicates this. That said, having 5 vpu's bind together, while involving certain a.a. changes, is not the stepping stone to life. Remember that viruses aren't considered life. You have to have protein complexes form before you can have life as we know it. Therefore, Behe thinks in terms of PTPBS between "kinds" of proteins.

Who are you trying to convince with this absurdity? It sounds like you are interpretting scripture rather than discussing science. "Kinds" of proteins? You are just making ad hoc reinterpretations of Behe's words.

So far we've had somebody say that HIV-2 vpx doesn't count because Behe was obviously talking about HIV-1 and not HIV-2 and now you're coming up with this bullshit about binding sites between Vpu subunits not counting because Behe obviously was talking about binding sites between different "kinds" of proteins.

Actually it was meant as an ad hoc conjecture.

And I guess you don't see the problem with inventing ad hoc excuses to avoid major problems?

You appear to have become frustrated and desperate.

Frustrated - yes. Desperate - no.

Really. Just answer my questions. Why doesn't Behe point to some mutation that is beyond the edge of evolution? Pick one. What mutation could not have occurred through natural means?

Torbjörn Larsson said...
This comment has been removed by the author.
Torbjörn Larsson said...

PaV:

why do you fight to prove that Behe is wrong about zero PTPBS when it comes to the mutational powerhouse that HIV is, and then turn around and fight to prove that he’s wrong to say that humans have come up with a PTPBS in such few replications when we aren’t mutational powerhouses?

It is hilarious to see you twisting and turning on the spit you put yourself on. You pass every error of Behe's we discover without so much as an acknowledgment, but complaints. (But spit out as much irrelevant data that you can find in a Gish gallop.)

Now, as far as I can see your obsession with the term "mutational powerhouse" comes from Behe using it to characterize HIV. You can't complain to us that it turns out humans evolve faster by the proxy Behe has chosen, nor that Behe knew that all along.

This isn't a matter so much of HIV expertise, of which I imagine Ian has lots of. It's about following the argument that Behe makes in EoE, and then critiquing it in a meaningful way.

Who's on first? The point is that Behe tries to criticize evolutionary theory, and fail to do so in a meaningful way. These threads were initiated by pointing out his factual errors on HIV in EoE.

Those are at least 10 and counting, including the major problem that his proxy for evolutionary rate is off by 12 orders of magnitude. You don't adress that, while you earlier was so exalted by these figures.

HIV, over the last two or three decades, has shown no signs of any biochemical novelty.

PaV's gap theory, find an uneventful time period and extrapolate. But you can see in the original posts that larger evolutionary changes happens over time.

Ian made a mistake confusing CD4 and CD8

You are making this up. What you claimed is that CD4, which was what Ian discussed, isn't a transmembrane protein. (But CD8 is.)

While I'm not interested enough to dig up the structure but can wait for Ian's professional reply, I can note that the ExPASy data base claims that both CD4 and CD8 are "single-pass type I membrane protein".

ERV said...

Cant stay-- gotta infect cells... CD4+ enriched T-cells... CD4, a transmembrane protein with FOUR Ig domains that did NOT (According to Behe) evolve from Ig.

*rolleyes*

PaV-- Now, if it's possible for just that one portion of sequencing to be captured by HIV, that's a different matter...
Im sorry, are you suffering from the Cottage Cheese Cordova reading disability?

PaV said...

Larsson says:

"It is hilarious to see you twisting and turning on the spit you put yourself on. You pass every error of Behe's we discover without so much as an acknowledgment, but complaints."

You nitpick what Behe has written. Why should I twist and turn. Your vulgarity is a sign of desperation.


"Now, as far as I can see your obsession with the term "mutational powerhouse" comes from Behe using it to characterize HIV. You can't complain to us that it turns out humans evolve faster by the proxy Behe has chosen, nor that Behe knew that all along."

I haven't been complaining at all. I've been pointing out the absurd position that has been taken; namely, that "we must prove Behe wrong about how many PTPBS have evolved in HIV" while at the same time being seemingly completely unaware that to say that humans have developed a PTPBS in a relatively small (compared to HIV and malaria) number of replications is a far more potent argument for the "power" of RM+NS.


"The point is that Behe tries to criticize evolutionary theory, and fail to do so in a meaningful way. These threads were initiated by pointing out his factual errors on HIV in EoE.

Please point out the factual error. Behe, in Table 7.1 says that HIV has not developed a PTPBS since that late 70's. Do you want to dispute that? Where's your evidence?

"Those are at least 10 and counting, including the major problem that his proxy for evolutionary rate is off by 12 orders of magnitude. You don't adress that, while you earlier was so exalted by these figures."

Yes, ten picayune issues, nitpicks. Great science, that.

It's not 12 orders of magnitude, it's 10^12 difference. But, remember, Behe is stating the facts. Some people can't handle the facts. I just pointed out the implication of what Behe writes, and what is Ian's reaction? He wants to say, "Sickle-cell is no PTPBS". Why not, instead, seize on the opening it gives? [Can I answer that question? Because we MUST prove Behe WRONG. We MUST. We MUST.]


"PaV:
HIV, over the last two or three decades, has shown no signs of any biochemical novelty.



Larsson responds:

"PaV's gap theory, find an uneventful time period and extrapolate. But you can see in the original posts that larger evolutionary changes happens over time."

A "mutational powerhouse" like HIV doesn't do anything for 10^20 replications, 30,000 more replications than elephants have had in their entire existence (the genome size of an elephant is approx. 10^9, while for HIV it's 10^4. So the numbers suggest that HIV has changed every position on its genome 5 times, and nothing happens, while the elephant has only had the chance to change all the positions along its genome twice, yet, somehow the elephant diverged from its LCA with [using Table 7.1 for humans] two PTPBS. Yeah. Right.) and this has no impact on you. How strange.

Larsson:

"You are making this up. What you claimed is that CD4, which was what Ian discussed, isn't a transmembrane protein. (But CD8 is.)

While I'm not interested enough to dig up the structure but can wait for Ian's professional reply, I can note that the ExPASy data base claims that both CD4 and CD8 are "single-pass type I membrane protein".


Since you've written this, I've double-checked Wikipedia. They have a drawing there of CD4 which is badly labeled (actually, it's hardly labeled). It gave the impression that the CD4, while anchored, did not go all the way through the cell membrane. I went to another place on Wikipedia and they had a very clear drawing showing that CD4 does, in fact, go through the cell membrane. That portion of CD4, the N-terminal, serves, as I said, as an anchor for CD4. Ian was suggesting in an earlier post that vpu was acting in the cell membrane to detach the CD4 from the cell membrane. The actual mechanism of how that happens hasn't been clearly stated though. In the review paper I referenced before, they say that it is the C-terminus that interacts with the CD4 receptor sites. So, does that mean that the C-terminus connects to the CD4 first, and then while connected to CD4 inserts its N-terminal alongside the CD4 anchor? I don't know. But given that vpu is viroporin, the same properties that the N-terminal has which lead to viroporin formation (and thus a "pore"), might be just the handy thing that vpu needs to "uproot" the CD4 from the cell membrane. IOW, vpu does in its monomer form pretty much what it does in its pentamer form. Now this has nothing to do with the argument against Behe. But it does suggest that claiming a PTPBS here or there can be a delicate matter, one that must be handled with care. But, of course, what is two, or three, or even five PTPBS when minimal protein complexes involve ten proteins (thus 9 PTPBS).

And thanks for the opportunity to correct my misimpression of CD4.

Smokey said...

PaV wrote:
"Remember I was citing a paper."

Not really. More accurately, you were misrepresenting and quote-mining a paper. Idiotically, you claimed that a review was "intriguing." Reviews are rarely intriguing. New data are intriguing, but reviews, by definition, don't have new data.

"In that paper they identified the hydrophobic, transmembrane portions of both proteins."

I could train an 8-year-old to do that. You're another story. No one who understands the basics would cite a paper as doing that.

"On that basis, I said the similarity was 8 out of 19, or 42%."

Yes, but you were dishonest in claiming that this "basis" represented 1) the similarity between the whole sequences, and 2) that it represented homology. You see, TM domains have lots of hydrophobic residues, and those are similar to each other. If you had bothered to do a BLAST (you know, that thang you lied about not being able to do from your computer, you would have realized how idiotic you were to claim that a 42% similarity between TM domains represented homology.

"But, afterwards--don't get old because small type throws you even with bi-focals!--I saw that it was 7 out of 19, or 37%."

On most browsers, there's a command for zooming in.

"So thanks for giving me the opportunity for correcting the mistake. And, again, I've posted that we're just seeing a homology of sequencing..."

We call it sequence similarity. Homology means that we've concluded common descent, which is what we're debating here.

"... that matches a homology in function, and no more. M2 and vpu are very dissimilar outside this one region. Now, if it's possible for just that one portion of sequencing to be captured by HIV, that's a different matter; but, as I said in response to you already, it was no more than an ad hoc conjecture in the first place."

It was utter bullshit, and you were called on it. Therefore, Behe was wrong.

"You nitpick what Behe has written."

No, YOU are nitpicking to reinterpret what he has written. Behe is a liar. Behe is afraid to test his hypotheses, and instead he lies, not only about the facts, but in misrepresenting his hypotheses as facts.

"Why should I twist and turn."

Why don't you tell us?

"Your vulgarity is a sign of desperation."

Our vulgarity is a fucking sign of contempt for the true obscenity of your endless dishonesty.

"Please point out the factual error. Behe, in Table 7.1 says that HIV has not developed a PTPBS since that late 70's. Do you want to dispute that? Where's your evidence?"

Where's Behe's evidence, you dishonest twat? Only a deliberately dishonest person would try and treat what Behe SAYS as the data.

"It's not 12 orders of magnitude, it's 10^12 difference."

That's exactly what 12 orders of magnitude means: a factor of 10^12. Behe even has a callout box in the book to explain scientific notation to ninnies like you, PaV. That's one of the few things he got right in the book!

"But, remember, Behe is stating the facts."

No, Behe is lying about many facts, and omits many, many important facts that would make his thesis laughable.

"Some people can't handle the facts."

That would be you and Behe. We real scientists not only handle the facts, we produce new facts. Behe produces no data at all.

"I just pointed out the implication of what Behe writes,..."

But you're assuming that what Behe writes is factual.

"A "mutational powerhouse" like HIV doesn't do anything for 10^20 replications,..."

You're lying. There are major biochemical changes within the infection of a single individual.

"So the numbers suggest that HIV has changed every position on its genome 5 times,..."

No, they don't. You're lying again.

"Since you've written this, I've double-checked Wikipedia."

You're lying again. You didn't double-check it, you finally checked it for the first time.

"They have a drawing there of CD4 which is badly labeled (actually, it's hardly labeled)."

Yet it was perfectly clear from that drawing that CD4 is a transmembrane protein. You just saw what you wanted to see.

"It gave the impression that the CD4, while anchored, did not go all the way through the cell membrane."

You're lying, PaV. The fault is all yours. None of the diagrams give that impression.

"That portion of CD4, the N-terminal, ..."

No, it's called the N-terminUS.

"... Ian was suggesting in an earlier post that vpu was acting in the cell membrane to detach the CD4 from the cell membrane."

I don't think so. Ian talked about degradation. YOU made that claim, not Ian. Who's mixed up, PaV?

"But, of course, what is two, or three, or even five PTPBS when minimal protein complexes involve ten proteins (thus 9 PTPBS)."

What?

"And thanks for the opportunity to correct my misimpression of CD4."

You misspelled "misrepresentation," and if you had a gram of integrity, you'd apologize for falsely accusing Ian of being mixed up.

ERV said...

Actually, PaV, Ive completely lost my patience with you after your last couple of posts.

In my original essay, there is a list of references. I made a conscious effort to use freely available papers whenever possible. If you were really interested in this topic, and you were really interested in my argument, this seems like the first place I would look, if I were you.

However, your last few posts betray the fact you did not read the papers I suggested, as several of them explain CD4 degredation in a very readable/understandable manner.

Which leads me to believe you arent at all interested in this topic. Youre interested in being contrary-- ie HIV should evolve a mustache, Behe meant 10 protein-protein interactions, and so on.

Why should anyone take the time to respond to you, when you wont take the time to educate yourself on this issue?

PaV said...

ERV:

"Why should anyone take the time to respond to you, when you wont take the time to educate yourself on this issue?"

ERV, you're looking at it from your perspective. I'm not an HIV researcher. I'm involved in lots of other things. When a discussion like this begins, I'm forced to learn a lot more about HIV than I would otherwise care to know---all of this in an effort to make sense out of what is being claimed. If I make a few mistakes along the way, I would think you might overlook them. From my perspective, I've had to spend an inordinate amount of time learning how to BLAST sequences, reading articles, searching for articles, reread EoE, and then what happens? I take a giant step backwards and find out that Behe never addressed the time period over which all these HIV changes occurred, making the whole argument, from my perspective, entirely moot. I have a sense of having wasted an extreme amount of time. Behe's facts are solid. Are they misleading? Perhaps, but in the end he concedes to RM+NS more than you can really demonstrate could happen within 10^20 replications.

IOW, I'm not too interested in CD4 degradation. The only point I would be concerned with would be whether vpu has evolved a new binding site or not. The rest is for researchers like you.

ERV said...

So on one hand, your just a poor poor gentleman trying to figure this crazy stuff out in your free time...

But on the OTHER hand you want to come in, fists flying, telling geneticists and virologists they dont understand genetics and virology.

Fantastic.

quantok said...

PaV said:

"...Behe never addressed the time period over which all these HIV changes occurred, making the whole argument, from my perspective, entirely moot. I have a sense of having wasted an extreme amount of time. Behe's facts are solid."

PaV, would it be fair to say that you think that Behe is factually solid on the point that HIV-1 has been doing nothing genome-wise since the 1970s and is therefore not evolving in any meaningful sense of the word?

Take a look again at the diagram in ERV's original post Michael Behe, please allow me to introduce myself... . It looks to my eye like HIV-1 wasn't doing anything genome-wise between the mid-1930s to the late 1950s.

Now just between us laymen who get all their information about virology and biochem from Wikipedia, doesn't that look like a cautionary tale? Wouldn't anyone using this long period of 'dormancy' as proof that the virus was incapable of evolving have looked like a bit of a prat by the time The Beatles were topping the charts? [And all this evoluting in a tiny number of infections, too}.

Of course, others on this blog can now point out just how much evoluting HIV has been doing while the Fab Four have been dying off in the wrong order. But even on Behe's own terms, his argument is no better than saying "I tossed a coin 100 times and never got 10 heads in a row — therefore it can't happen no matter how many times I toss the coin".

art said...

PaV, Behe's book was entitled "The Edge of Evolution", not "The Edge of Evolution of E. coli, malaria, and HIV in humans in the last 30 years". He's making claims about all of biology. One of these claims - that HIV has not developed new protein-protein interactions - is plainly wrong. It's wrong even for the time period you think Behe limits himself to, but its wrong in general terms.

Think about it - you're claiming that Behe would have no problems with multiple "CCC"'s evolving in one time period of a few decades, but not another. This makes no sense, and these are words I would not put in Behe's mouth.

And you should be interested in CD4 degradation. There're two more "CCC"'s that defy Behe's assertions. (To boot, they take you into a fascinating world of regulation that blows ID perceptions of biology totally out of the water.)

Smokey said...

art wrote:
"(To boot, they take you into a fascinating world of regulation that blows ID perceptions of biology totally out of the water.)"

art, we both know that ID perceptions of biology can explain any existing data and somehow twist them to work in favor of ID, but strangely enough, ID perceptions of biology do not enable a single ID proponent to make clear-cut predictions about future data.

art said...

Earlier, I said to PaV:

Think about it - you're claiming that Behe would have no problems with multiple "CCC"'s evolving in one time period of a few decades, but not another. This makes no sense, and these are words I would not put in Behe's mouth.

OK, so maybe yer not saying exactly this. But that is how your comments are reading to me. If you mean something else, PaV, you should clarify things. In particular, you need to make it clear why the "Behe was only talking about HIV in humans in a span of 30 years" (or however long you want to make it) spiel is not the dodge that I (and others here) believe it is.

Ian Musgrave said...

Pav Wrote:
The bold face a.a. match up. For M2, 8 out of 19 a.a. line up with the vpu sequence. That’s 42% similarity. Here’s what you said Ian: “In terms of sequence, there is no significant sequence similarity between M2 and Vpu
.

I have a hard time deciding if you are deeply dishonest, or just deeply clueless about biology, despite your claims to be a biologically trained. No one with a shred of integrity, or biological understanding, would do what you have, which is to take two sub-sections from different parts of two molecules, manually align them ignoring all but one short subsequence, then express the percentage of identity with the shortest segment and then compare it with figures for the whole protein (and not do a statistical analysis into the bargin, what is it about statistics you don't get).

The paper in question is Gonzalez ME, Carrasco L. FEBS Lett. 2003 Sep 18;552(1):28-34. Viroporins. (no free full text, sorry).

Its quite clear in the paper that the hydrophobic regions you compare are located in different places in Vpu (N terminal) vs M2 (centre). As the paper is not freely available I reproduce the proteins below. The top sequence is the hydrophobic HIV Vpu sequence from the paper; the second sequence is the hydrophobic M2 sequence from the paper. The X’s are the amino acids given in the paper and missing from PaV’s alignment. I’ve arranged them on the MAFF alignment’s I’ve generated and the –‘s represents gaps put in by the program to get optimal alignment. I’ve also distorted the optimal alignment so I can line up the LVV sequence PaV has aligned, which is why the lengths don’t align. You can immediately see that the hydrophobic sections are in different position in the molecule, MAFF had to put in a dirty big gap to get bits of the hydrophobic sections to match. This is already a clue that PaV has gone badly wrong. If you line things up like PaV has, and calculate on the basis of the HIV Vpu sequence length, then the similarity is an unimpressive 26% for the hydrophobic section alone (the fact that the similarities are not symmetrical is an issue that I won’t explore for space reasons). But it gets worse.

MQP-IQI-----AI---------------VALVVAIIIAIVVWSIVIIXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX-X-XXXXXXXXXXXXXXXXXXXXXX
xxx-xxx-----xxxxxxxxxxxxxxxxxxPLVVAASIIGILHLILWILXXXXXXXXXXXXX----------XXXXXXXXXXXXXXXXXX-X-XXXXXXXXXXXXXXXXXXXXXX
MQL-LEI-----IS--------------IAALVIVAIIAIVVWTIVGIEYRRILRQRKIDRLIDRITERAEDSGNESDGDQEELSA-L-VEMGHHAPWDVND--------L
MLL-LIK-----LG--------------FIGLAIETLIVIVVWAIVYRIYREVKVEEKISQLRQRIRDRAEDSGNESDGDAEELAN-L-LPPDRIDQDNWV

The third sequence is another Vpu sequence (I’ve used HIV-1-M-b sequences here). You can see it doesn’t have the LVVA sequence found in Influenza M2, the similarities between the hydrophic regions in the Vpu sequence is a really poor 19%. And I haven’t chosen the least matching HIV sequence; I just grabbed a fairly typical b class sequence. Oh, what else is missing from our equation, why the SIV-Vpu hydrophobic sequence of course. If we compare the hydrophobic sequence from a randomly chosen SIV with a HIV Vpu we see a massive 44% agreement. So once again, just comparing the hydrophobic regions, SIV Vpu and HIV Vpu are more similar than HIV Vpu and M2. For PaV’s idea to be correct only the hydrophobic channel section from middle of M2 has to be swapped into the front of Vpu, then the highly conserved VVW sequence seen in HIV and SIV Vpu has to reappear spontaneously. Very likely, whereas the SIV sequence gaining a couple of V’s and an A is SOOOO unlikely – not (checking the structures of the non-viroporin forming HIV-1-O and HIV-1-N shows a progressive gain of the features that will eventually make the viroporin).

MNS-LDI-----VA------------------IVGLVVAFIAAIVVWTIVYIEYRKIRKQRKIDRLIDRIAERAEDSGNESDGDQEELSA-L-VEMGHHAPWDVDD--------L
MQL-LEI-----IS------------------IAALVIVAIIAIVVWTIVGIEYRRILRQRKIDRLIDRIAERAEDSGNESDGDQEELSA-L-VEMGHHAPWDVDD--------L
MQL-LEI-----IS------------------IAALVIVAIIAIVVWTIVGIEYRRILRQRKIDRLIDRITERAEDSGNESDGDQEELSA-L-VEMGHHAPWDVND--------L
MQA-LQI-----SA------------------IVGLVVAAIIAIVVWTIVFIEYRKILRQKKIDRLIDRIRERAEDSGNESEGDQEELSA-L-VEMGHHAPWDVDD--------L
MQL-LAI-----LA------------------IVGLVVAAILAIVVWFIVFIEYKKILKQRKIDRLIDRIIERAEDSGNESDGDQEELSA-F-VEGGYRAPWDVND--------L
MPP-LQV-----LA------------------VVALVVAAIIAIVVWTIVFIEYRKILRQRRIDRLLERIRDRAEDSGNESDGDQEELSA-L-VERGHLAPWDVND--------L
MQS-LET-----LG------------------IVALVVAFILAIIVWTIVFIEYRKIRKQKRIDRLIQRISERAEDSGNESEGDEEALAA-L-VGMGHLAPWDVDD--------L
MSL-LTE-----VETPIRNEWGCRCNDSSDPLVVAANIIGILHLILWILDRLFFKCVYRLFK----------HGLKRGPSTEGVPESMRE-E-YRKEQQNAVDADDSHFVSIELE
MSL-LTE-----VETPIRNEWGCRCNDSSDPLVVAASIIGILHLILWILDRLFFKCVYRLFK----------HGLKRGPSTEGVPESMRE-E-YRKEQQNAVDADDSHFVSIELE
MSL-LTE-----VETPIRNEWGCRCNDSSDPLVVAASIIGILHLILWILDRLFFKCVYRLFK----------HGLKRGPSTEGVPESMRE-E-YRKEQQNAVDADDSHFVSIELE
MSL-LTE-----VETPIRNEWGCRCNDSSDPLVVAASIIGIVHLILWIIDRLFSKSIYRIFK----------HGLKRGPSTEGVPESMRE-E-YREEQQNAVDADDGHFVSIELE
MSL-LTE-----VETPIRNEWGCRCNDSSDPLVVAASIIGIVHLILWIIDRLFSKSIYRIFK----------HGLKRGPSTEGVPESMRE-E-YREEQQNAVDADDGHFVSIELE
MSL-LNE-----VETPIRNEWGCRCNDSSDPLVVAASIIGIVHLILWIIDRLFFKCIYRIFK----------HGLKRGPSTEGVPESMRE-E-YREEQQNAVDADEGHFVSIQLE

I’ve also included full alignments from MAFF for a few HIV-Vpu and M2 channels (I’ve done alignments on much large numbers of viruses, but they don’t read well in comments. You will notice in the optimized alignments, the LVVAA sequence doesn’t get aligned between HIV Vpu and M2, why is that you ask, because you have to optimize for the entire protein, and shuffling things along to match the LVVA sections throws the rest of the proteins out of whack. If you look at the full sequences, you can also see that a lot of viroporin forming Vpu’s don’t have the M2 LVVA, which suggests that it is not the determinant of ion channel activity in Vpu, whereas every M2 protein I have a sequence for has the sequence LVVAA.

Anyway, the point is that even when PaV seriously distorts the data, and tries to compare short, sub-sequences from different sections of Vpu and M2, and then uses and apples and oranges comparison with full sequence alignments to make the M2 match look better, SIV Vpu still is a better match for HIV Vpu than M2.

Now, I’ve just spent a huge amount of time and space explaining something that should be obvious to anyone with just a smidgen of biological knowledge. Vpu is not M2, it’s not even a transferred section of M2. We can put this one to bed now.

Now PaV, having gone to all this trouble on one minor point, can you give me one reason PaV, why I should put any effort into correcting your other distortions and misrepresentations? Can you give me any assurance that you will not go to ludicrous biologically ignorant lengths to try and defend Behe on the other points? I have other things to do, and I don’t want to waste my time on someone who is willfully mendacious.

Torbjörn Larsson said...
This comment has been removed by the author.
Torbjörn Larsson said...

Catching up on threads.

PaV:

I agree with Smokey that you are intentionally misrepresenting, and ERV that you are a contrarian goalpost mover. This will therefore probably be my last comment, a response to you and some challenges you should meet before I will listen to you.

Your vulgarity is a sign of desperation.

It was an humoristic characterization. Do you want me to show you vulgar? :-P

You nitpick what Behe has written.

I catch him on factual errors. Some central to his ideas - such as mutation rates being off 10^12 times, something that concerns you in your repeated attempts of irrelevant probability calculations. Some embarrassing - such as claiming his biggest running EoE example P. falciparum having IFT genes, or HIV containing DNA.

When those facts torpedoes his central thesis, he or you need to respond.

I've been pointing out the absurd position that has been taken

Moving goalposts much? We are discussing HIV. But we all know Behe is mistaken on other points, and you have let us uncover some of those.

Please point out the factual error.

I have pointed out 10 in this thread. Feel free to respond if you care about Behe's ideas.

It's not 12 orders of magnitude, it's 10^12 difference.

12 decades are 12 orders of magnitude, you ignorant [insert chosen vulgarity nere].

Now, this trivially invalidates Behe's claim by his own data. Your inability to respond is telling - Behe's ideas mean nothing to you.

A "mutational powerhouse" like HIV doesn't do anything for 10^20 replications

You persist in your or Behe's characterization. Fine, show us why HIV is worse than other viruses.

It does not do nothing, it mutates and selects in response on contingent fitness pressures (such as new antiretrovirals) as you can see from the graph. So 6 major events since 1930 would with the correct number, 10^14 individuals in 10 years, become 1 major evolutionary event for ~ 10^14 individuals. This is consistent with Ian Musgraves 2 new protein-protein binding sites in 10 years.

Note that humans evolve faster, at least 1 new (and probably many more) protein-protein binding site in perhaps 10^8 individuals. (Behe's numbers.)

How strange.

What is strange is that you can't distinguish between asexual and sexual populations with their different evolutionary mechanisms.

I've double-checked Wikipedia. ... thanks for the opportunity to correct my misimpression

Oh, science by Wikipedia. Sure, I can believe that of Behe too, that would explain his scholarship. During Dover he confessed to not study literature much.

But you are welcome.

PaV said...

I have a hard time deciding if you are deeply dishonest, or just deeply clueless about biology, despite your claims to be a biologically trained.

I claimed to have a degree in biology. And I didn’t say I got it within the last ten years.

No one with a shred of integrity, or biological understanding, would do what you have, which is to take two sub-sections from different parts of two molecules, manually align them ignoring all but one short subsequence, then express the percentage of identity with the shortest segment and then compare it with figures for the whole protein (and not do a statistical analysis into the bargin, what is it about statistics you don't get).

This is an obvious overstatement. Is this some kind of peer-reviewed blog? Am I submitting my conjecture as a paper?

And, please tell me, why is it wrong to line up the C-terminus side of M2 and vpu? And, please tell me, why is it wrong, and unconscionable, to overlook the final portion of vpu that has no corresponding part to the hydrophobic region in M2? Or, to put it another way, if M2 sets up an ‘ion-channel’ with its 19 hydrophobic a.a.’s, then why should we believe that vpu needs more. M2 and vpu are different types of transmembrane proteins, and from what I’ve seen, vpu, being a type I, could very well, even likely have, a signal portion attached to its hydrophobic portion. Finally, then, I see nothing wrong with comparing the portions of vpu and M2 that obviously match up; AND, it seems to make more sense to do so from the C-terminus side since that marks the end of the penetration of BOTH proteins into the membrane.

The paper in question is Gonzalez ME, Carrasco L. FEBS Lett. 2003 Sep 18;552(1):28-34. Viroporins. (no free full text, sorry).

Well, guess what? I downloaded the paper----for free. Maybe it was just my lucky day, but you can try and get the paper here.

Its quite clear in the paper that the hydrophobic regions you compare are located in different places in Vpu (N terminus) vs M2 (centre).

I’ve already given an explanation for the alignment I chose.

As the paper is not freely available I reproduce the proteins below. The top sequence is the hydrophobic HIV Vpu sequence from the paper; the second sequence is the hydrophobic M2 sequence from the paper. The X’s are the amino acids given in the paper and missing from PaV’s alignment. I’ve arranged them on the MAFF alignment’s I’ve generated and the –‘s represents gaps put in by the program to get optimal alignment. I’ve also distorted the optimal alignment so I can line up the LVV sequence PaV has aligned, which is why the lengths don’t align. You can immediately see that the hydrophobic sections are in different position in the molecule, MAFF had to put in a dirty big gap to get bits of the hydrophobic sections to match. This is already a clue that PaV has gone badly wrong.

I’ll stop you here, Ian. I think what the “dirty big gap” illustrates is the silliness of trying to force these sequences through some program that is designed to line up given sequences ‘no matter the consequence’. You know the expression: “Junk in; junk out.” You’re simply forcing a fit----for whatever reason.

If you line things up like PaV has, and calculate on the basis of the HIV Vpu sequence length, then the similarity is an unimpressive 26% for the hydrophobic section alone (the fact that the similarities are not symmetrical is an issue that I won’t explore for space reasons). But it gets worse.

You’ve forced a fit on top of another forced-fit. Why don’t you just align the two hydrophobic regions from the C-terminus ends moving towards the N-terminus end, then you’ll get 7/19 = 37%


MQP-IQI-----AI---------------VALVVAIIIAIVVWSIVIIXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX-X-XXXXXXXXXXXXXXXXXXXXXX
xxx-xxx-----xxxxxxxxxxxxxxxxxxPLVVAASIIGILHLILWILXXXXXXXXXXXXX----------XXXXXXXXXXXXXXXXXX-X-XXXXXXXXXXXXXXXXXXXXXX
MQL-LEI-----IS--------------IAALVIVAIIAIVVWTIVGIEYRRILRQRKIDRLIDRITERAEDSGNESDGDQEELSA-L-VEMGHHAPWDVND--------L
MLL-LIK-----LG--------------FIGLAIETLIVIVVWAIVYRIYREVKVEEKISQLRQRIRDRAEDSGNESDGDAEELAN-L-LPPDRIDQDNWV

The third sequence is another Vpu sequence (I’ve used HIV-1-M-b sequences here). You can see it doesn’t have the LVVA sequence found in Influenza M2, the similarities between the hydrophic regions in the Vpu sequence is a really poor 19%. And I haven’t chosen the least matching HIV sequence; I just grabbed a fairly typical b class sequence.


This is now getting real interesting, Ian. You can go to PubMed and ask for “HIV-1 M” protein sequences. I looked at four, three had the LVVA sequence right there, between positions #12-15. I matched up this region with M2. Guess what? It comes out to 7/19 = 37%. Ian, are we looking at the same sequences? Fairly typical b class sequence?

Oh, what else is missing from our equation, why the SIV-Vpu hydrophobic sequence of course. If we compare the hydrophobic sequence from a randomly chosen SIV with a HIV Vpu we see a massive 44% agreement.

Really, Ian. When I compared them, the best fit (out of about 4) had 7 out of 28 a.a.’s lined up. That’s 25%. How did you arrive at 44% ?


So once again, just comparing the hydrophobic regions, SIV Vpu and HIV Vpu are more similar than HIV Vpu and M2.

That’s not what I come up with. I come up with the opposite.

For PaV’s idea to be correct only the hydrophobic channel section from middle of M2 has to be swapped into the front of Vpu, then the highly conserved VVW sequence seen in HIV and SIV Vpu has to reappear spontaneously.


Help me out, Ian. When I compared a SIVvpu and the vpu sequence Carrasco shows, lining the “VVW” sequences, I get 4 out of 28 matches. Not very good. And, it’s VVW in HIV, but VVG in the SIV I looked at (that matched at all).

Very likely, whereas the SIV sequence gaining a couple of V’s and an A is SOOOO unlikely – not (checking the structures of the non-viroporin forming HIV-1-O and HIV-1-N shows a progressive gain of the features that will eventually make the viroporin).

MNS-LDI-----VA------------------IVGLVVAFIAAIVVWTIVYIEYRKIRKQRKIDRLIDRIAERAEDSGNESDGDQEELSA-L-VEMGHHAPWDVDD--------L
MQL-LEI-----IS------------------IAALVIVAIIAIVVWTIVGIEYRRILRQRKIDRLIDRIAERAEDSGNESDGDQEELSA-L-VEMGHHAPWDVDD--------L
MQL-LEI-----IS------------------IAALVIVAIIAIVVWTIVGIEYRRILRQRKIDRLIDRITERAEDSGNESDGDQEELSA-L-VEMGHHAPWDVND--------L
MQA-LQI-----SA------------------IVGLVVAAIIAIVVWTIVFIEYRKILRQKKIDRLIDRIRERAEDSGNESEGDQEELSA-L-VEMGHHAPWDVDD--------L
MQL-LAI-----LA------------------IVGLVVAAILAIVVWFIVFIEYKKILKQRKIDRLIDRIIERAEDSGNESDGDQEELSA-F-VEGGYRAPWDVND--------L
MPP-LQV-----LA------------------VVALVVAAIIAIVVWTIVFIEYRKILRQRRIDRLLERIRDRAEDSGNESDGDQEELSA-L-VERGHLAPWDVND--------L
MQS-LET-----LG------------------IVALVVAFILAIIVWTIVFIEYRKIRKQKRIDRLIQRISERAEDSGNESEGDEEALAA-L-VGMGHLAPWDVDD--------L
MSL-LTE-----VETPIRNEWGCRCNDSSDPLVVAANIIGILHLILWILDRLFFKCVYRLFK----------HGLKRGPSTEGVPESMRE-E-YRKEQQNAVDADDSHFVSIELE
MSL-LTE-----VETPIRNEWGCRCNDSSDPLVVAASIIGILHLILWILDRLFFKCVYRLFK----------HGLKRGPSTEGVPESMRE-E-YRKEQQNAVDADDSHFVSIELE
MSL-LTE-----VETPIRNEWGCRCNDSSDPLVVAASIIGILHLILWILDRLFFKCVYRLFK----------HGLKRGPSTEGVPESMRE-E-YRKEQQNAVDADDSHFVSIELE
MSL-LTE-----VETPIRNEWGCRCNDSSDPLVVAASIIGIVHLILWIIDRLFSKSIYRIFK----------HGLKRGPSTEGVPESMRE-E-YREEQQNAVDADDGHFVSIELE
MSL-LTE-----VETPIRNEWGCRCNDSSDPLVVAASIIGIVHLILWIIDRLFSKSIYRIFK----------HGLKRGPSTEGVPESMRE-E-YREEQQNAVDADDGHFVSIELE
MSL-LNE-----VETPIRNEWGCRCNDSSDPLVVAASIIGIVHLILWIIDRLFFKCIYRIFK----------HGLKRGPSTEGVPESMRE-E-YREEQQNAVDADEGHFVSIQLE


Help me out again, Ian.

When I look at sequence line #2, I see LVIVA. So, isn’t the logical conclusion either that N and O inserted an isoleucine, or that N dropped it? One, single, deletion. That’s all. The same is seen in sequence lines #5 and #8.

Now look at lines #11,14,17,20,23,27,31,35,38, and 41. I see the entire M2 hydrophobic sequence, starting with XLVVA. The sequences start out fine, but don’t end up fine. There should be something like a WIL ending, with the isoleucine (I) being a critical match up between vpu and M2. We see instead, for the most part, that this isoleucine is either not there, or out of position. This might be the reason why the N and O’s don’t form ‘ion-channels’. So, here’s a great experiment for the wise: clip out the matching sequences in vpu M, N and O that align with M2, and then see which ones form ion-channels in a lipid by-layer, which ones don’t. Then try inserting a isoleucine in the 18th position of the M2 hydrophobic region, and see if this restores its ‘ion-channel’ capacity. And, for sequences that are LVIVA, delete the isoleucine, and see what happens.

Finally, Ian, when you compare vpus from HIV viruses this results in all kinds of spacing having to be introduced by MAFF--for roughly the SAME protein---doesn't that give you a hint that maybe MAFF is spewing out junk?

I’ve also included full alignments from MAFF for a few HIV-Vpu and M2 channels (I’ve done alignments on much large numbers of viruses, but they don’t read well in comments. You will notice in the optimized alignments, the LVVAA sequence doesn’t get aligned between HIV Vpu and M2, why is that you ask, because you have to optimize for the entire protein, and shuffling things along to match the LVVA sections throws the rest of the proteins out of whack.

Remember: “Junk in; junk out”.

If you look at the full sequences, you can also see that a lot of viroporin forming Vpu’s don’t have the M2 LVVA, which suggests that it is not the determinant of ion channel activity in Vpu, whereas every M2 protein I have a sequence for has the sequence LVVAA.

Ian, when I go to PubMed, and ask for HIV-1 M vpu’s, almost every one I looked at had the LVVA. One had LVIV, but that could have been a vpu from a N or O that was wrongly put in with the M’s; or it could simply be an artifact of the PCR method (which, presumably, is how these sequences are arrived at)


Anyway, the point is that even when PaV seriously distorts the data, and tries to compare short, sub-sequences from different sections of Vpu and M2, and then uses and apples and oranges comparison with full sequence alignments to make the M2 match look better, SIV Vpu still is a better match for HIV Vpu than M2.

That’s not what I see, Ian.

Now, I’ve just spent a huge amount of time and space explaining something that should be obvious to anyone with just a smidgen of biological knowledge. Vpu is not M2, it’s not even a transferred section of M2. We can put this one to bed now.

In an earlier post, I said that M2 and vpu are "not" the same protein/gene. They don’t match up except for the hydrophobic portions (How interesting, though!) There’s a very clear highly-conserved portion right in the middle of vpu, from about position #50 to #60: EDSGNESEGD, which is a clear marker for vpu-HIV (even the simian lines are fairly similar). But, Ian, you have in no way ruled out that the hydrophobic regions of M2 and vpu are unrelated. If you simply look at Carrasco’s paper on viroporins, and the hydrophobic regions shown, the only two regions that have any similarity are those of vpu and M2.

Here’s a quote I included in an earlier post: “Taken together, these results indicate for the first time that the TM domain of the Vpu protein can be functionally substituted with the TM of M2 of influenza A virus.” And here’s another: “For example, the size, hydropathicity, and domain structure of the membrane-associated influenza virus M2 protein (15, 26) and the foot-and-mouth disease virus protein p3A (5) are strikingly similar to those of vpu.

There’s some fruit ready for the picking here, Ian. Are you going to let your bias towards anything ID get in the way?

Now PaV, having gone to all this trouble on one minor point, can you give me one reason PaV, why I should put any effort into correcting your other distortions and misrepresentations? Can you give me any assurance that you will not go to ludicrous biologically ignorant lengths to try and defend Behe on the other points? I have other things to do, and I don’t want to waste my time on someone who is willfully mendacious.

Well, Ian, based on what my research has shown, and using common sense thinking, you have some explaining to do. And, are you trying to do to me what you’re trying to do to Behe: that is, he’s wrong about this particular thing “here”, so he must be wrong about all kinds of other things; AND, since I’m the one who’s pointed it out, “trust me”, I’ll lead you to green pastures.

Sorry, I don’t buy any of this.

"Willfully mendacious"? I'm sorry, that doesn't apply to me.

Ian Musgrave said...

PaV wrote: "Willfully mendacious"? I'm sorry, that doesn't apply to me.

Sure does.

Pav wrote: Finally, Ian, when you compare vpus from HIV viruses this results in all kinds of spacing having to be introduced by MAFF--for roughly the SAME protein---doesn't that give you a hint that maybe MAFF is spewing out junk?

No, it tells me you haven’t the faintest clue about sequence alignment. The alignments I presented were for Vpu and M2, not only HIV Vpu. When you try and align Vpu and M2, there will be huge gaps as 1) the proteins are of different sizes and 2) the hydrophobic region in Vpu is at the start of the molecule and the hydrophobic region in M2 is in the middle of the molecule. So of course, if you want anything except the LVVA sequence to line up, you have to introduce gaps (otherwise you have part of the hydrophobic section of Vpu sitting on top of a decidedly non-hydrophobic section of M2, which makes the overall similarity much worse).

Now, if you line up only HIV-Vpu’s or even HIV-SIV Vpu’s, most of the gaps disappear. Not all will, if you include HIV-1-M-c sequences there is an extra group of amino acids only in HIV-1-M-c in the hydrophobic region, so it is longer than the others (if this turns out to be an ion-gating switch, it will be a fourth protein-protein binding site the Behe has missed). But the main point is that if you try and align HIV Vpu and Influenza M2, you get huge gaps in the alignment because they are so dissimilar, if you align HIV Vpu and SIV Vpu you get very few gaps, because they are so similar.

As a reality check, looking at the sequences LVVA and IVVW over 55 balanced HIV-1 sequences, LVVA has a conservation score of 5.5 (poorly conserved, as most HIV viruses don’t have LVVA) and IVVW has a conservation score of 9.5 (highly conserved). In Influenza M2 LVVAA (note the extra A, in HIV this extra A is missing) is invariant (conservation score of 10) over 50 sequences from humans, pigs, birds etc. taken from several different timeframes, while IVVW is not present at all. SIV either has IVVW or a conserved variant (eg IVIW) of it in most cases. Once again, HIV and M2 have different structures and SIV is closest to the viroporin coding HIV’s, not M2.

Aligning HIV, SIV and N2 using colour coding for conservation shows that HIV and SIV have much higher percentage identity in the helix region, let alone anywhere else. Sure you can cherry pick any sequence to find ones that match up better or worse, but that is why I have done multiple sequence alignments over 50-55 viruses to make sure that my conclusions are valid. I’ve even cut out the hydrophobic regions and just aligned them. Once again, M2 is an out-group to SIV-HIV, whereas if you are correct that just the hyprodrophobic regions were swapped, than the hydrophobic region should nest within the pore forming HIV-Vpu’s. It doesn’t (unfortunately, I can’t post pictures of alignments, or my CONSURF results, and as blogger doesn’t allow PRE of CODE tags, I can’t show the alignments properly).

Take home message. Don’t fool with sequence alignments when you don’t know what you are doing. Don’t try and snow someone who is in the middle of co-authoring a sequence alignment paper, and who actually knows sequence alignment (and the tools involved).

HIV-Vpu evolved from SIV-Vpu, it is not a swapped in M2 or a sub-segment of M2. End of story. Now stop wasting our time.

Ian Musgrave said...

I don't know why I am doing this, perhaps because I just learnt that a review I co-authored is number 1 in the top 25 hottest papers at BBA molecular basis of disease and I'm feeling in a good mood..

Anyway, I used PSI-blast to try and align the hydrophobic region of of M2 to HIV-Vpu. PSI-blast is an iterative fitting alignment program which is more sensitive than standard BLAST (I tried running standard "align 2 sequences BLAST" for just the hydrophobic regions of M2 and Vpu, but the "no statistical signficance message" got old pretty fast).

I used the H3N2 and H1N1 M2 sequences as they are pretty representative of all the others.

After 7 rounds of PSI-Blast fitting, M2 hydrophobic region showed no statistically signifcant match to any Vpu.

Whereas running the hydrophobic region from SIV Vpus'pulled up HIV Vpu's either imediately or on the first iteration (typical signficance values were 3.4E-0.06, that is seriously significant) or the first or second iteration.

I don't know if this will work, this is a distance tree of the result. If it does come up (it might vanish after a few days), then you have to set the drop down menu Max Seq Difference 0.7 to see named tree branches. Note how HIV-Vpu's all nest within the SIV sequences. If HIV-Vpu had gained a hydrophobic region from M2, it would be an outgroup.

Anyway, we can put the whole M2 thing to bed now. The statistics show clearly that the hydrophobic region of SIV-Vpu's is statistically similar to HIV-Vpu's, while there is absolutely no statistical match between M2 hydrophobic regions and any Vpu.

Chris Noble said...

PaV, I'll ask again. Who are you trying to convince?

It obviously isn't Ian, ERV or anyone else that actually understands the subject.

The arrogance is typical of creationists. One day they are completely ignorant about the difference between functional homology and sequence similarity and the next day they're lecturing scientists who do research in this field.

Who are you trying to convince? Fellow creationists? Yourself?

Ian Musgrave said...

If you want to understand PSI-BLAST (and why gapped alignments are generated), the paper is here.

You can run PSI-Blast from here.

quantok said...

Ian, this has been a fascinating insight into the kind of scientific work you do, but I wonder if both you and PaV have forgotten PaV's original speculation at the beginning of this thread?

PaV stated: "It would be easy, I think, to simply suppose that somewhere along the line that SIV picked up the M2 from a chimp that was infected with Type A Influenza."

So all your sequencing may indeed have proved that "HIV-Vpu evolved from SIV-Vpu, it is not a swapped in M2 or a sub-segment of M2", but that isn't what PaV hoped was true. PaV claimed that the viroporin is in SIV and that it came from influenza M2 before SIV-Vpu entered humans.

Of course, since SIV-Vpu isn't a viroporin he would have to further assume that the SIV-Vpu we now observe 'degraded' somehow after it had passed its ion-channel function into humans.

But what's another epicycle amongst friends? Let's not forget the whole point of these speculative musings: to preserve Behe's claim that HIV evolution is a damp squib. In fact, PaV hedges his bets: either HIV-Vpu viroporin was already there in chimps, or, of it did arise in humans "It appears the basic chemistry of the Vpu, like the M2, spontaenously form such an 'ion channel'... The fact that the 'ion channel' seems to form spontaneously minimizes any supposed complexity that we want to attribute to Vpu on the basis of its forming a viroporin."

So either the clever evoluting bit happened in another virus (uncomfortable thought!) or (phew!), there is an illusion of irreducible complexity in the viroporin and it's really just a biochemical inevitability.

Chris Noble asked PaV: "Who are you trying to convince? Fellow creationists? Yourself?"

PaV has already given us the answer: "...here is this fabulous replicator, fabulous mutator, and yet it really hasn't moved much has it? Can we isolate any kind of "intermediate form"? No. It's a virus. All the subtypes are viruses."

That someone could think an intermediate form of a virus might be a non-virus tells you all you need to know. PaV's audience, like any supporter of ID, is the typical under-16 Answers in Genesis reader, nothing more.

Ian Musgrave said...

quantok wrote: PaV claimed that the viroporin is in SIV and that it came from influenza M2 before SIV-Vpu entered humans.

Still doesn't work. Then SIV Vpu and M2 should nest together, and they don't

art said...

But what if HIV/VPu picked up just the small transmembrane segment from M2? Would one still expect VPu and M2 to nest together, if one uses the complete amino acid sequences?

I asked Abbie before, because this is the sort of informed opinion that helps even more (or not) to refute claims such as are made by PaV - just what is known about the recombination rates between HIV and cellular or other RNAs, such as may be in a cell doubly-infected with HIV and influenza? Based on the biology (can one virus super- or co- infect cells infected with the other?), molecular biology (recombination rates and the like), and cell biology (do the two viruses replicate in somewhat isolated compartments or viroplasms?), how probable is the scenario that PaV is invoking in his attempt to rescue Behe?

Ian Musgrave said...

art wrote: But what if HIV/VPu picked up just the small transmembrane segment from M2? Would one still expect VPu and M2 to nest together, if one uses the complete amino acid sequences?

SFX: polite cough. That was the whole point of this post where I compared just the hydrophobic/transmembrane segments of M2 with the hydrophobic transmembrane segments of Vpu's (as well as whole Vpu's). No match at all, whereas the SIV Vpu transmembrane segements do match. The segments should nest, they don't.

See also this post which set up the preliinaries (and create FASTA files of just the hydrophobic regions.

Bottom line, comparing just the hydrophobic/transmembrane sections from HIV-Vpu, SIV Vpu and M2 refutes PaV's thesis.

PaV said...

IM:

As a reality check, looking at the sequences LVVA and IVVW over 55 balanced HIV-1 sequences, LVVA has a conservation score of 5.5 (poorly conserved, as most HIV viruses don’t have LVVA) and IVVW has a conservation score of 9.5 (highly conserved). In Influenza M2 LVVAA (note the extra A, in HIV this extra A is missing) is invariant (conservation score of 10) over 50 sequences from humans, pigs, birds etc. taken from several different timeframes, while IVVW is not present at all. SIV either has IVVW or a conserved variant (eg IVIW) of it in most cases. Once again, HIV and M2 have different structures and SIV is closest to the viroporin coding HIV’s, not M2.

Four things. First, the conserved sequence in vpu’s is AIVVW. This will be a point to bear in mind later on. Second, you should specify SIV as SIVcpz, because that has IVIW, whereas I don’t see in it regular SIV. However, if we specify SIVcpz, then, looking at its vpu, how do we know that HIV vpu developed from it, and not the other way around? Where, and how, did the “hand-off” take place? Is one direction obviously favored over another? I don’t have the answer. I’m just asking the question. Third, here are three sequences for vpu HIV-1-O, gotten from NCBI:

vpu hiv-1 group O

ORIGIN
1 mhhrdllvli iisalllinv iiwmfilrqy leqkkqdrre rdilerlrri aeikddsdye
61 sneeeeqevr dlihshgfdn pmfel
ORIGIN
1 mhhrdlltli iisallflnv ilwtfvlnky leqkkqdrre reilerlrri reikddsdye
61 sdgeeeqevm dlvhdygfdn pmfel
ORIGIN
1 mlhrnlllsi iisallltni ilwmyilrry leqrkqdsre reilerlrri reirddsdye
61 sneeeeqevr gqlvhnfgfd npmfel

According to your last post, these don’t form viroporins. I notice three things: first, AIVVW, nor IVVW can be found; second, I see LIIISA, but I don’t see anything like LVVA, which is what is seen in the Group M, subtype b vpu. In fact, relative to the closest thing to a I-AIVVW motif, we find ALLL where we would expect LVVA. So, both are lost, more or less. Third, “the” conserved sequence for vpu identification is 50-60: EDSGNESDGD. Where is it in type O? Here we have it that vpu for HIV-1-O is almost not recognizable as vpu for HIV, while vpu from SIVcpz is similar in many respects. So, again, when and how did the “hand-off” take place?

Lastly, yes, AIVVW is conserved throughout most of vpu (we just saw that it isn’t in type O). In looking at many, many sequences over these last few days, I notice that for different “subtypes”, the LVVA of Group M, subtype b, is disturbed. You’ll see LIVA, e.g., or LVIVA, or LIIA, etc. And the a.a. that would fall in the fifth spot of LVVAA, also varies with different “subtypes”. So, it seems as if changing this motif results in the different subtypes of vpu. There’s some variant subtype of vpu that is labeled CRO which invariably can be identified by LIVA, for example.

Here’s a sequence for SIVcpz:

1 mdivqqvgll vv(liie)lv(iv iviw)vkvykl ckedrrqkki drliarirer aedsgnesdg
61 dteelqdlit egdnlmhigi rdnrnn

I’ve emphasized the LIIE. Yes, it’s in the right position to match up with the LVVA of Grp M-b vpu, since we can see a I-AIVVW similarity right after that (also emphasized). Remember, for vpu HIV-1-O, the corresponding group is ALLL. And one of the variants of vpu-HIV I’ve seen is something like LIIA. And, it's very similar to type-O's LIIS.


Ian M:
Take home message. . . .
HIV-Vpu evolved from SIV-Vpu, it is not a swapped in M2 or a sub-segment of M2. End of story. Now stop wasting our time.


Your take home message is that M2 and the TM portion of vpu are so dissimilar that the suggestion that part of the TM of vpu came from M2 is ludicrous.

Well, it turns out that other scientists don’t share your opinion. In fact, they’ve taken the similarity very seriously. (Go here ) In fact, so seriously, that they’ve constructed a chimeric vpu which has the TM portion of M2 in place of vpu’s. Well, what happened when they did that? Two things: first, viral replication took place as usual; second, ion-channel activity also took place.

Here’s from the abstract:

“We constructed chimeric vpu gene in which the transmembrane domain of Vpu was replaced with that of the M2 protein of influenza. This chimeric vpu gene was substituted for the vpu gene in the genome of a pathogenic simian human immunodeficiency virus, SHIVKU-1bMC33. The resulting virus, SHIVM2, synthesized a Vpu protein that had a slightly different Mr compared to the parental SHIVKU-1bMC33, reflecting the different sizes of the two Vpu proteins. The SHIVM2 was shown to replicate with slightly reduced kinetics when compared to the parental SHIVKU-1bMC33 but electron microscopy revealed that the site of maturation was similar to the parental virus SHIVKU1bMC33. We show that the replication and spread of SHIVM2 could be blocked with the antiviral drug rimantadine, which is known to target the M2 ion channel. . . . Taken together, these results indicate for the first time that the TM domain of the Vpu protein can be functionally substituted with the TM of M2 of influenza A virus . . .”

So, Ian, not only CAN the M2 transmembrane be swapped into vpu, it HAS!

These same authors constructed a SHIV that had a motif ending with tryptophan (w). They had noticed that in M2 rimantidine affected the H-X-X-X-W portion of M2, which gives M2 its ‘ion-channel’ ability. So, in their SHIV they had a A-I-L-V-W motif. They substituted a histidine for the alanine, now giving it a H-X-X-X-W (H-I-L-V-W) motif like that of M2. Rimantidine was now able to shut down the ‘ion-channel’ activity. What do you know!

There’s another paper I read dealing with MD simulations of vpu. In the paper they suggest that what gives vpu’s ion-channel a ‘gated’ effect is the rotation of Helix 1 so that the tryptophan (that ‘w’ again) would turn towards the pore while a serine turns away. They also state this:

“The mechanisms of Vpu function are via protein-protein interaction and ion channel activity. Both functions seem to be independently allocated with either one of two distinct structural elements; the cytoplasmic domain or the TM domain.”

Also, they write:

“However, the ultimate effect of a viroporin, leading to cell death by uncontrolled increase of permeability, has not been found so far.”

This is a 2003 paper. Has it been confirmed that vpu is a viroporin in the interim? I don’t know, Ian. Perhaps you do.

Notice that the authors, obviously with a very deep biochemical background, distinguish between “protein-protein interactions” and “ion channel activity”. Doesn’t this get us all the way back to the very beginning, when I was challenging your assertions that viroporin formation represents “protein-protein” interactions (binding sites)? And their suggestion that rotation is involved suggests that the “gate” is not about a “protein-protein” interaction. That leaves us with CD4+ degradation. Fine.

Personally, I think this dead horse has been beaten enough.

ERV said...

PvM-- They MADE that construct. I MAKE HIV that has dsRED2 inserted into the HIV genome. That does not mean that HIV infected sea anemones and stole dsRED.

AND will you please READ MY BLOG?

PaV said...

quantok:

"So all your sequencing may indeed have proved that "HIV-Vpu evolved from SIV-Vpu, it is not a swapped in M2 or a sub-segment of M2", but that isn't what PaV hoped was true. PaV claimed that the viroporin is in SIV and that it came from influenza M2 before SIV-Vpu entered humans."

Thanks for reminding me of my original conjecture. We've been on a scenic tour in the interim.

In my last post, I showed that the marker for vpu, the EDSGNESDGD string, is present in SIVcpz. However, we don't see much similarity between SIVcpz and M2. I see two possible scenarios: (1) SIVcpz enters humans  humans are infected with influenza A (which, IIRC, simians are immune to)  M2 is picked up by vpu, conferring its ion channel activity, and then it diversifies  subtype O losses its ion channel capability and its vpu marker or, (2) SIVcpz enters humans  HIV is formed  type O diversifies from HIV, losing its EDSGNESDGD marker  HIV-M picks up M2 from the Spanish flu epdemic, and then diversifies into other groups and subtypes through recombination events. If I have been careful, all the pertinent facts are accounted for.

Having reread this post (prior to posting), I think I favor the second scenario since we can have SIVcpz and HIV together for some time (we don't know exactly, I'm supposing, when SIVcpz entered humans), long enough for Grp O to lose the marker, and then, with two different strains of HIV, the M2 enters the HIV-1 line, and Grp O stays the same.

chris noble:

”PaV, I'll ask again. Who are you trying to convince?”


I’m not trying to necessarily convince anyone. I’m waiting to BE convinced. Remember, this is ERV’s and Ian’s argument/claim. I’m asking questions. And sometimes the answers I’m given are very clear and very logical, and that’s that. But when the answers I’m given don’t satisfy me intellectually, well, naturally, I’m going to clarify the ways in which I disagree and ask more questions (even if they’re implicit).

PaV said...

ERV:

PvM-- They MADE that construct. I MAKE HIV that has dsRED2 inserted into the HIV genome. That does not mean that HIV infected sea anemones and stole dsRED.
"


I'm guessing you meant PaV. What has been shown is that it is possible to "replace" the TM of vpu and to "substitute" the TM of M2 for it. When you "insert" dsRED2 into vpu have you taken out something else that was functional? I bet not. What is demonstrated is that it is biologically relevant to swap out the TM of vpu for that of M2. M2, pretty much, works the same way. If we are now looking at vpu--part of the "mutational powerhouse" that is HIV, with its great powers of recombination--and see shifted segments that no longer "align", is that surprising? My answer would be no. But, hey, I don't write papers on sequencing either. (I'm not one, however, to accept things on "authority").

P.S. I either stay here and respond, or go off and play golf. If you don't hear from me for a while, you'll know what I decided to do. Cheers.

Chris Noble said...

Well, it turns out that other scientists don’t share your opinion. In fact, they’ve taken the similarity very seriously.

Before you have the arrogance to put words into the mouths of scientists who you don't know you should at least understand the subject.

There is a difference between functional homology and sequence similarity.

The authors of the paper that you cite do not state or even imply that HIV swapped genes with influenzavirus.

I'll give you the same advice that I give to HIV denialists who do the same type of pubjacking. Write to the authors of the paper and see whether they agree with your interpretation of the paper.

quantok said...

PaV, let me see if I understand what your mature position is.

1) HIV Vpu acquired its viroporin properties from the influenza virus. It did so by the classic evolutionary mechanism of genetic transfer. Authors of papers noting functional similarities between M2, the foot & mouth virus and HIV Vpu have failed to spot the common origin, but you did not.

2) HIV Vpu, after acquiring flu RNA, has undergone significant evolutionary changes masking the common origin of its viroporin function. These changes occurred in such a way as to scramble the sequence similarity with M2 whilst preserving its ion channel function. (A proton channel function in M2 also appears to have been lost).

3) Nothing has been said about HIV gaining Golgi binding properties or membrane binding function.

So, in conclusion, the claim that HIV acquired a major new property by an evolutionary mechanism other than random mutation of its own genome supports your observation that HIV is "...this fabulous replicator, fabulous mutator, and yet it really hasn't moved much has it?, hence preserving Behe's claim that HIV has acquired no significant new biochemical properties.

Now, can you explain why this refrain keeps going through my head: my Toyota has a carburettor. My bank manager's Mercedes has a carburettor. Ergo my Toyota is a Mercedes.

art said...

Ian,

Now do you see why I asked?

quantok said...

And in a parallel universe nearby...

ID: Random mutation can't increase information in the genome!

EVO: But it's not the only mechanism. Look at gene duplication or gene transfer.

ID: Give me one example!

EVO: Well, it's highly likely that HIV-1 gained its viroporin property by grabbing a segment of RNA from the influenza virus.

ID: You're just confusing functional similarities and inferring common descent. Look, the sequences don't even align!

EVO: But the genome has changed in the intervening decades and the evidence of common descent has been obscured.

ID: ROFL! It's just another bloody just-so story.

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