Wednesday, March 14, 2007

Deniers vs ERVs: Round 1, TKO

You know I was comfortable with Deniers going after HIV and Creationists going after ERVs, but over the past couple of weeks Ive learned that Deniers want to get their garlicy lemon-juice fingers into both of my research topics. A reader (far more patient than I) and Chris Noble (also more patient than I) have brought some of their specific claims to my attention, but lets just shut this nonsense down once and for all in one sentence. One sentence. It took me five posts to 'get' the Creationists ERV game. This turned out to be a lot easier.

"Lentiviruses and deltaretroviruses also share the distinction of being the only retroviral genera for which endogenous counterparts have not been identified."
The Evolution, Distribution and Diversity of Endogenous Retroviruses

Okay I lied, two sentences (really its just the same sentence again).
"No delta or lentivirus representatives were found among ERVs."
Use of Endogenous Retroviral Sequences (ERVs) and structural markers for retroviral phylogenetic inference and taxonomy

One of the funny things about viruses is that no matter how you classify them, one in a group will always be vastly different from another in that same group. Try classifying all viruses by their genomes-- but would you rather have a wart (HPV- DNA virus) or Hepatits B (also a DNA virus)? Their replication cycles are vastly different! Well, surely like, viruses with the same name are similar, like HSV-1 and HHV-6? Nope. Both herpes, but they infect totally different cells. Hmm. Well, maybe classify viruses by the types of tissue they infect-- Compare Hepatitis B (double stranded DNA virus) with Hepatitis C (single stranded +RNA virus). Totally different creatures.

So if you dont study retroviruses, you wouldnt know that there are currently seven different kinds of retroviruses: alpha-, beta-, gamma-, delta-, epsilon-, lenti-, spuma-. If you dont study endogenous retroviruses, you would think that theyre all essentially the same thing. They arent. To put this into perspective, when you hear Culshaw/Duesberg/et al talking about how HIV is an ERV, imagine theyre saying that a chimpanzee is really a humpback whale. Theyre both mammals, right? HIV and ERVs are both retroviruses, right?

There are no lentiviral ERVs, thus HIV cannot be an ERV.

Whats particularly troubling to me about this whole scenario is that I didnt know this information 24 hours ago. I mean I figured you could classify ERVs into the seven groups, but I didnt know there were no lentiviral (or delta-) ERVs. I just stumbled upon this info this morning while playing on PubMed (technically I was doing a literature review, but when work is fun, its playing). I didnt put in any weird, unique search terms. This means that 'trained' Professional Deniers are making these asinine comments without even bothering to do a PubMed search before they say anything! Theyre THAT arrogant! Well, theyre either arrogant, or they know damn well what the literature says and they prefer to be Professional Jackasses like Professional Creationists (no, I dont believe Behe, Dembski, etc believe a word they say).

Anyway, next time you hear one of them say something about HIV-->ERV say "Chimpanzee--> Whale." There. Now we can expect Deniers to stop saying shit about ERVs, right?

.... Right?

**faint sounds of a Creationist talking about the second law of thermodynamics**



drpsduke said...

HIV:HERV-K roughly 44% identity (gag-pol-env)

Human: Hamster 87% identity (EF-2 gene)
Human: Yeast 60% identity (EF-2 gene)
Human:Chicken 85% identity (EF-2 gene)
Human: Fruit fly 71% identity (EF-2 gene)
Human: Euglena gracilis 57% identity (EF-2 gene)
Human: Methanobacterium thermoautotrophicum 38% identity (EF-2 gene)
Human:E. coli 31% Identity (EF-2 vs EF-G, fusA gene)

So HIV --> ERV is more like
primate --> Euglena

Anonymous said...

Good point, drpsduke. But are you looking at protein or nucleic acid? I can't even get a 44% identity between HIV and HERV-K by nucleic acid. In fact, to put it in scientific terms, it's really damn low!

drpsduke said...

The absolute numbers come out different for DNA (just 4 bases, so any two random sequences tend to be roughly 25% identical) or protein (20 amino acids, so 25% identity can be significant), but either way, the relative distances between these organisms is the same.

The numbers I presented were in fact DNA % identity, that is why I said "gene" not "protein".

For protein, I don't have all of gag-pol-env aligned, only the Pol protease-RT-integrase regions. The Protein % Identity between HERV-K and HIV-1 is 20.4% and Similarity calculated with a PAM250 similarity matrix is 38.5%.

The human : Methanococcus EF-2 protein comparison comes out at 26.5% Identity and 45.5% PAM250 Similarity.

Of course the alignment used (adding gaps to both sequences to get an "optimal" alignment) is not trivial. The researchers who run the PFAM database are very good and producing multiple sequence alignments for protein families. So using their alignments of protein to guide the DNA alignment is a key.

Anonymous said...

i was using more unsophisticated methods that didn't introduce many gaps in the dna.

Anonymous said...

Haha, this site is somebody's idea of a joke, right, comparing genomic elements to fruit flies and such.

So a pol gene within a human genome that codes for integrase, protease, polymerase incorporation of dNTPs into DNA using an RNA template and ribonuclease H digestion of the RNA template is as different from a pol gene with these functions in a lentivirus as a chicken from a bacterium?

Nick Naylor

drpsduke said...

Hi Nick,

It is no joke. Different genes withing the same organism evolve at different rate. For example in retroviruses, the Pol gene is highly conserved because it has a complex catalytic core to bind RNA/DNA nucleotides etc, plus the RNAase end and all that. Envelope tends to evolve very fast to escape the host immune system. So even if the underlying mutation rate is equal across the genome, positive and negative selection result in variable evolution rates.

Rates of evolution vary hugely between organisms, depending on the mutation rate (RNA genomes are unstable, and reverse transcription very error-prone compared to the proof-reading DNA polymerase in eukaryotic nuclei), selection pressures, population sizes, reproductive rates and many other factors.

Not all genes with similarity are homologous. Homology is a binary yes/no state. If two things shared a common ancestor they are homologous, if they did not, they are not homologous. Similarity is most often due to homology, but can sometimes be due to convergent evolution.

There are many clues, beyond sequence similarity, that all retroviruses shared a common ancestor, probably some sort of retroposon that replicated (I can't quite say "lived") hundreds of millions of years ago. All retroviruses have the same LTR-Gag-Pol-Env-LTR genome organization. As far as I know (there could be exceptions I don't know about) the pol gene usually encodes protease, reverse transcritpase, sometimes a dUTPase, RNAase H, and integrase in that order.

Many genes/proteins found in eukaryotes clearly have homologs in both eubacteria and archaebacteria. But those many genes, such as DNApolymerases, RNA polymerases, some ribosomal proteins, transfer-RNA genes, etc. are still a small percentage of all genes. The other genes may or may not have homologs in all three urkingdoms, they have evolved so far that we can no longer recognize any significant similarity. The little similarity they share could be the result of convergence.

Most genes/proteins have bits and pieces that have clearly recombined. So we find the same tyrosine kinase domain "recycled" into hundreds of different proteins in the mammalian genome:
The some of those may get the tyrosine kinase domain swapped out for a serine/threonine kinase domain. Much evolution happens by such re-shuffling of gene segments, rather than by single point mutations.

It's all very fascinating, once you get into it, and realize that we now have the complete genomes of human, chimpanzee, dog, cat, pig, horse, cow, chicken, several yeasts, dozens of plants, thousands of bacteria, etc to analyze.

The data collection is now far exceeding the rate we can analyze it at even a crude level, thanks to the robots and technologies developed in the 1990s to sequence the human genome.

ERV said...

Thank you, drpsduke, but I think Anon#2 was just confused about which genes you were comparing... But s/he wasnt exactly clear, so maybe theyll come back to explain themselves a bit better?

And thanks for the comparisons duke and Anon#1! However that didnt exactly cheer me up lol!!