New evolutionary mechanism found in primates

Photo credit Bald Wonder

Photo credit Bald Wonder

Researchers at Cornell University in New York and Bar-Ilan University in Israel found a new mechanism for gene mutation based on a family of virus-fighting enzymes called APOBECs. The interesting thing about APOBECs is that they fight viruses sort of the same way viruses fight us–they make changes to the viral genome until the virus gives up and can’t keep attacking anymore.

Some viruses, like HIV and influenza, evade our defenses by mutating themselves. We can keep getting the flu year after year because the virus comes back with just enough changes to its genome that it is unrecognizable to our immune system. The equivalent of a fake mustache and a trench coat is enough of a change to slip past the body’s defenses and make us sick. Again.

APOBECs turn the tables, bombarding the viral genome with more changes than it can handle. Maybe it can still infect and reproduce with a fake mustache and trench coat, but with enough mutations it turns into something that can’t cause illness anymore.

The potential downside is that the mutation attack can become friendly fire, and turn against its own cells, leading to cancer. What the Cornell team learned is that the friendly fire self-mutation attack can create mutations that are passed on to progeny. That means that a defense system meant to disable attacking viruses could also be a force for evolution.

The researchers looked a type of APOBEC specific to primates, called APOBEC3. Because APOBEC3 creates a specific pattern to its mutations, they were able to see thousands of incidences of APOBEC3 in primate genomes, and that activity was over-represented in functional regions.

That means that when APOBEC3 went on a friendly fire frenzy, and attacked a functional region of the primate genome, that change was somehow maintained. Typically, one of three things happens when DNA in a functional region is mutated. First, it could be very, very bad and lead to pretty much immediate death or nonviability of the organism. Those changes are obviously not passed down through the generations. Second, it might make zero difference. Those changes could be passed on, but they tend not to be maintained and conserved in the genome. Last, the change could be advantageous. The presence of many changes by APOBEC3 that have been maintained and passed on through the generations in the primate genome implies that those changes were evolutionarily advantageous.

This really shakes up older theories of how evolution happens. Mutations are supposed to happen at random on a fairly predictable schedule, and species divergence estimates have been based on that assumption.

I reached out to Cornell to ask for more information about the implications of this study, and Postdoctoral Research Associate Aaron Sams explained,

“The typical way of thinking about the timing of divergence is as a ‘molecular clock.’  We think of most mutations as arising individually and randomly over time. If we assume that the process that generates these mutations is essentially random, and we know a rate at which that process generates those random mutations, then we can use the number of mutations that accumulate between two species to estimate the amount of time that has passed since their divergence.”

APOBEC3 is specific to primates, so I asked Aaron if that means primate evolution is different in any way. Like, are primates in some way the influenza among vertebrates? Sams says…maybe.

“That’s a great question, but we don’t really know. It is something that we would like to know though. I am inclined to doubt that this process would lead to faster evolution in primates in general, but it could be possible that APOBECs could drive faster evolution in particular regions of the genome, a single gene or set of genes for instance.
It still isn’t clear to us if the types of mutation clusters that we identified accumulated in bursts, or accumulated more or less gradually. The lead authors of this paper, Yishay Pinto and Orshay Gabay, are working to better understand these types of questions.”
The study was published in Genome Research.