Wednesday, April 04, 2007

Moble Elements, Drivers of Genomic Evolution Part Deux

I didnt mean to make this a two parter (obviously, as 'Part One' was written several months ago), but I just came upon this article, and TEs impact on genomic evolution obviously needs another post. Its not just the TEs themselves that have directed the evolution of our genomes-- how our genomes have reacted to TEs has also had far reaching effects.

As my blogs subtitle goes, if we're made in Gods image, 'God' is made of gag, pol, and env. Up to 50% of our genome is made of transposable elements. Theyre egotistical bits of parasitic DNA that only care about themselves. Invite themselves into our genome, eat all our brownies, and leave the place a mess-- inserting themselves in protein coding regions, breaking chromosomes, rearranging genes and chromosomes, messing up splicing, and screwing up transcription levels.

So, how are we still alive right now? If ~50% of our genome is made of these bastards, how is everything still working? Cause our genome evolved ways to make 'God' shut up. Lots of ways, actually, as Ive alluded to in my posts to Creationists and Deniers that want ERVs, in particular, to be active.

RNAi - A cellular function probably almost as old as TEs themselves. Maybe... *maybe*... RNAi was initially 'invented' strictly for control of TEs, and was eventually co-opted for use by the cell itself. See, most TEs have a little inverted repeat at the beginning and the end of their genome, so a transcript would invert itself into an RNA hairpin-- exactly what dicers love to eat.
Experimental evidence of this control mechanism is that if you screw up RNAi proteins in eukaryotes, transcript levels of TEs jumps up. It also appears that C. elegans use the RNAi pathway as their main means of keeping TEs quiet.

Epigenetics -
Making changes to histones causes DNA to twist up around them tight, or loosen up. Keep your DNA locked up tight, and genes arent transcribed, including TEs.
You can also make DNA wrap up around histones tighter by making little changes to DNA, called DNA methylation. Again, keeping the DNA wound up tight keeps the transcription machinery from getting in and making TE transcripts.
And, you can use chromatin remodeling proteins (like SWI/SNF in plants) to alter the structure of your chromatin, changing the loops and supercoils of your double-stranded DNA.

RNAi AND Epigenetics, Wondertwins, UNITE! - In some eukaryotes, RNAi is required for chromatin modifications, like in fission yeast. Sometimes RNAi and chromatin remodeling combine to actually cut out TEs, like in Tetrahymena and Paramecium!

So I missed half the picture in that first post!

13 comments:

Chris Harrison said...

I love me some transposable elements.

But seriously Abby, cool post. I think you're the only person who can make these degenerate chunks of DNA appealing.
It's as if you turned a mentally retarded guy into the prom king.

ERV said...

I have an ulterior motive. One of my first posts is about Patrick Forterre, a fellow who thinks we evolved from and because of viruses.

Im of the same opinion, and Im casually trying to convince you all that he's on the right track ;)

The Factician said...

I'm not certain on this (it's been a while since I read much about speciation) but I think that a lot of evolutionary biologists think that speciation events are driven by all kinds of pathogens (viruses and bacterial).

drpsduke said...

Taking the joke too far...

Our genomes contain many repetitive elements, ERVs, and transposable elements. However, to imply that anything close to 50% is transposable is not right.

I have seen no solid evidence that Alu repeats and many other types of repeats are transposable. However, I have not searched for such evidence, so if you know of it, fill me in please.

It is my gut feeling that the duplication of elements is more important than their tranposability. One we have two copies of a sequence of any type on the same chromosome, it is simple for recombination to occur during meiosis or mitosis to remove the region between the repeats from one copy of the chromosome and add an extra copy to the other copy being made.

Duplicated genes, such as our hemoglobin gene cluster, allow different copies to evolve to different functions, one for fetal globin and one for adult globin, for example.

There are quite clearly hundreds to thousands of different types of "mutational events" from fusion of two complete genomes to make tetraploids (as is common in plants), to duplication of whole chromosomes (trisomy 21 is an example in humans) down to single base substitutions. All of these are involved in evolution, and it is never quite right to suggest that any one of them is the "most important" of "the one" that drove or allowed evolution of developmental regulation (to get multicellular organisms in which not all cells are identical).

The Factician said...

drpsduke,

In fact Alu elements are usually not transposable. The vast majority of them are dead (i.e. they've become truncated or mutated into oblivion). But they are from a family of autonomous and non-autonomous transposable elements (non-autonomous basically means they require proteins from another element to be able to move).

erv got it right in her post, around 50% of the genome is dead transposable elements. Work in the Kazazian lab at UPenn has helped to identify which of the (very few) of them is active. If you ever have the chance, he gives a pretty good talk...

paul said...

Another cool mechanism in N. crassa that may be a defense mechanism against TEs (with other neat implications as well).

http://scienceweek.com/2003/sc031010-3.htm

Tyler DiPietro said...

"One of my first posts is about Patrick Forterre, a fellow who thinks we evolved from and because of viruses."

Being the idiot non-biologist here, I find myself wondering what impact this would have on the role endosymbiotic invasion and capture plays on evolution. I know we are all disappointed in Lynn Margulis because of her recent HIV denialism, but what do you think of her ideas outside of that, Abby?

Kristjan Wager said...

Guys, it's Abbie, not Abby, at least according to our hostress' comment over at Pharyngula.

ERV, did you see the news about rabies vaccinations protecting test animals against AIDS-like diseases? I werote a little about it over at my blog, but I'm sure you could write something much more intelligent about it.

drpsduke said...

OK. I guess the point I wanted to make was not so much about what percent of the mammalian genome (it's not just humans that carry this stuff) or vertebrate genome is composed of remnants of elements that once were able to move/duplicate.

It was more that bacteria and most other life forms also carry some of the same things. So it is not like transposons are the single reason why humans see mammals as "higher" than all the other organisms.

Also, I wanted to make sure that people understand that even the ones that are still "active" don't jump around on a daily or monthly basis. It is more like one jump every million years or even longer.

There are a lot of people advocating the "theories" of Mae Wan Ho and her "fluid genome" stuff. Quite simply, the evidence from comparing the chimpanzee complete genome, to the human complete genome does not support the idea of a "fluid genome" of the type she advocates.

The Factician said...

One hop every million years? Try one hop every time you make a sperm. The active transposons in the human genome range from fairly inactive to active, but all of the ones that have been detected to be active are hopping *right now as we speak*. Transposons don't hop on the "every million years" scenarion. If they did, they'd already have accumulated enough mutations in them to be dead. Keep in mind that every time the human genome replicates itself (every single cell division) you are making several errors - most of them inconsequential, but nonetheless.

Transposons hop. Alot.

In terms of uniqueness? Your average bacteria has less than 1% of its genome as transposons - though most of theirs is active. They're much more efficient at ridding themselves of parasitic DNA.

There are folks trying to ask how important transposons are to biology. Jef Boeke is trying to knock out every transposon in yeast (and Fred Blattner has already done it for E. coli). I look forward to the day that synthetic biology allows us to do that experiment in mice...

ERV said...

Oh I see youre points, duke! Of the ~50% of our genome that is of TE origin, only the ones that still have the ability to move/transcribe need to be controlled with RNAi and epigenetics. Certainly a majority of these bits have been taken care of the old fashioned way- mutation into junk.

And, the chromosomal rearrangement bit is what I was trying to write about in that first post-- how sequence similarities in TEs allowed for neat chromosomal rearrangements and duplications/deletions/etc. Thats totally a biggie! This post was more of an addendum: "Oh yeah! We used TEs to Red Queen RNAi and epigenetics!"

And I didnt mean to imply that TEs have only been involved in human evolution-- Theyre in everything!

paul, tyler, kris-- Im gonna have to look into all that stuff, thanks!

(hehehe And it is 'Abbie', technically, but its a nickname, so Im not neurotic about it)

Chris Harrison said...

Oops. I'm sorry for misspelling your nickname Abbie.
And thanks to Kristjan for correcting me.

drpsduke said...

OK. Maybe some of the active transposons do move once every week or once every month. But most of those movements are detrimental to the individual (and only movements in the sperm or egg; germ line; will be passed on to offspring) so the transposion movements that are successfully passed on to many future generations are much much more rare than all transposon movements.

The point I am attempting to make, is only that there have been some 5 or 12 million years since we shared a common ancestor with gorillas and chimpanzees, and our genomes are not "scrambled" with respect to their genomes.

Even between primates and rodents, with perhaps some 40 to 60 million years of separation, there are large chunks of chromosomes that are still contiguously homologous.

The other point, was that bacteria, fungi, single-cell eukaryotic protists, and plants also have movable elements in their genomes. So it is not simply the acquisition of transposons or ERVs that has allowed multicellular differentiation to evolve.

Surely they do move about, and surely that does help speed up evolution, by aiding gene duplication etc. rather than just waiting for point mutations to generate new genes. But they are not the single reason for evolution, they only contribute to it.