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Trade-offs in defense against retroviruses

I have written about evolutionary trade-offs before, starting with early posts about trade-offs between seed size and seed number in plants, and trade-offs between the ability of insects to escape predators by flying away, versus the ability to hide from them by playing dead. I have also given some examples of the increasing use of sophisticated experimental (often molecular) methods in evolutionary biology. This week's paper combines both themes.

The paper is "Restriction of an extinct retrovirus by the human TRIM5-alpha antiviral protein" by Shari Kaiser, Harmit Malik, and Michael Emerman, published in Science (vol.316 p.1756).

Retroviruses are made of RNA, but make DNA copies of themselves that can insert into the DNA of host cells they infect. HIV, the cause of AIDS, is a well-known example, but there are many others. If DNA copies of the retrovirus are inserted into cells giving rise to sperm or eggs, they can be passed to the next generation, as endogenous retroviruses. If the DNA inserts somewhere where it turns an important gene on or off, it may kill the host. Or, once in a while, this change may turn out to be beneficial. The few beneficial changes are the ones that survive and spread, just as the few mutations that are beneficial are the ones that persist.

VWXYNot has an interesting discussion of how a creationist web site misused one of her papers as evidence of "intelligent design." She shows how shared endoviruses can be used to infer shared ancestry, providing yet more evidence that we share a recent ancestor with apes, less-recent ancestors with monkeys, etc. But that's not what this week's paper is about....

...except that the retrovirus it discusses is found in chimps and gorillas, but not in humans. Did our common ancestor somehow pass this endogenous retrovirus, PtERV, on to chimps and gorillas, but not to us? That seems unlikely, since each of them has multiple copies. How could we miss inheriting some of them, if they came from an ancestor shared by all three species?

In fact, if this difference in retrovirus infection were the only information we had about humans, chimps, and gorillas, it would make me wonder whether chimps might be more closely related to gorillas than they are to us. Then, they could both have inherited PtERV from an ancestor they share with each other, but not with us. But most modern family trees put chimps and humans together, on a separate branch from gorillas, so I'd look first for another explanation...

...and, as Deep Thought once said, "there is an answer; a simple answer." The chimps and gorillas didn't inherit the endogenous retrovirus from a common ancestor. By comparing the viral-origin DNA in chimps and gorillas, the authors estimate that they picked it up 3-4 million years ago. Although this is 1000 times longer ago than some religion-based estimates of the age of the earth, it is only one-thousandth the actual age of the earth. It was about the time when Lucy lived, and at least a million years after the last common ancestor of humans and chimps lived. So, their ancestors living at that time caught the virus; ours didn't. [See comments for additional evidence for this.]

But why didn't we? 3-4 million years ago, the (nonshared) ancestors of humans, chimps, and gorillas were all living in Africa, perhaps near each other. Could our ancestors have somehow been more resistant to this virus than theirs? That's the main question answered by this paper.

Ideally, the authors would have resurrected some 3-million-year-old virus to test. This probably would have involved crossing rope bridges, being chased by tigers (not ordinarily found in Africa, but maybe escaped from a zoo?), and stealing a bit of amber (containing mosquitoes that had bitten chimps) from a Mayan temple (don't ask me how that got to Africa). But, instead, they decided to resurrect the original PtERV virus from endogenous retroviruses in modern chimps.

Mutations over the last 3-4 million years have changed each individual copy in the chimp genome, but there are enough copies per chimp that they were able to figure out the original DNA sequence. They made a hybrid virus containing the original RNA sequence from PtERV, particularly for that part of the virus targeted by a defense protein, TRIM5-alpha, found in all apes, including humans.

They then tested whether this virus could infect cells with the human version of TRIM5-alpha, or those from various apes and monkeys. Most apes and monkeys were susceptible to the PtERV virus, but modern humans, modern chimps, and modern sooty mangabeys were resistant. Because chimp DNA is full of "fossil" endogenous retroviruses, we know that their ancestors 3-4 million years ago must have been susceptible, but they've apparently evolved resistance since then. We just beat them to it. Clever of us...

...except that all the species that are most resistant to PtERV are also highly susceptible to infection by HIV. They were able to identify a specific region in our TRIM5-alpha gene that determines specificity in virus defense. One sequence gives resistance to PtERV, another to HIV. Take your choice.

But, would it spoil some vast eternal plan if we had two different copies of TRIM5-alpha? Would that give resistance to both viruses? While we're at it, wouldn't it be nice if we had a different genetic code (for translating DNA into protein) from all other animals? We'd still be able to digest their proteins (same amino acids), but any virus that could reproduce in them wouldn't be able to reproduce in us, because it would make nonfunctional proteins (different amino acid order). Of course, if humans had a different genetic code, that would make it really obvious that we had been created separately from other life, which would undermine the need for faith... "and vanished in a puff of logic."


Wow, that's a really cool paper. I have to admit I haven't read it properly yet, but I certainly will now!

I assume that they found the same kind of virus in chimps and in gorillas, but that the insertions weren't orthologous (i.e. in the same exact places in the genome)?

Good point. It's highly unlikely they would have insertions in the same place except by inheritance from a common ancestor. I don't remember seeing anything about that in the paper.

You're IT :)

The relevant details are in the original 2005 paper from Evan Eichler's group, who publish lots of really cool work. Open access at http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0030110.

~96% of insertions were unambiguously NOT orthologous, i.e. they were inserted in completely different areas in different species. Of the remainder, it seemed likely that most were also non-orthologous, but there were some problems mapping the insertion sites to a high enough resolution. So it looks like the different species that contain PtERVs acquired them independently, rather than by inheritance from a common ancestor.

So if the ERV is not present in Humans but it is present in Chimps and Gorillas then the chimps and gorillas were infected independently, and we were resistant.

But if we had it too then that would prove that we all had a common ancestor.

Either I am missing the point or it seems awfully convenient to conclude that the chimp and the gorilla independently became infected rather than THEY had a common ancestor and we did not.

I presume there is other evidence to exclude this possibility.


Thanks for your comment, but yes, you are missing the point. Try reading the whole post again more slowly, including the part about chimps and gorillas having picked up the virus millions of years after our common ancestors.

The hypothesis that gorillas split off before the common ancestor of chimps and humans is based on lots of gene comparisons, not just one.



I think it is obvious that many functional sequences in the human genome COULD have been inserted by ERVs, but I am skeptical of the 8% number. What are the assumptions? And could the ERV have actually taken the DNA out of the human in the first place, and so the common RNA might have originated in the human? Just asking.

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