A human T cell (blue) is under attack by HIV (yellow), the virus that causes AIDS.          SciTechDaily

What events have most shaped our human genomes since the split of our ancestors from the ancestors of chimpanzees? What has been the main driving force for human gene evolution? Climate comes to mind; nutrition also; ecology is linked to both. Then there’s social interaction which has driven the evolution of social intelligence. But the one factor that stands out, according to a recent eLIFE paper whose lead author is David Enard from Stanford University, is our interaction with viruses. Viruses have driven over 30% of all the adaptive amino acid changes (non-synonymous mutations) in our genomes, and are the most potent drivers of evolutionary change across mammalian genomes in general.

One would expect that a number of proteins associated with the immune system and viral defense would be likely targets for selection pressure over eons. Enard, for instance, cites the case of the gene PKR (protein kinase R) which is one of the fastest adaptively evolving proteins in all mammals since it recognises viral RNA and blocks viral replication in host cells. Indeed, very few cases of adaptation to viruses are known among non-immune system genes,  making the case of transferrin, which governs intake of iron into cells, an exception to this rule. But, when you think about it, viruses are notorious for hijacking many aspects of cell biology as they pervert normal cellular function into the new task of making more virus, and Enard and his team have discovered that transferrin is only one among many non-immune system genes affected by viruses – a very wide range of proteins, which they call virus-interacting proteins (VIPs), which govern many aspects of cellular machinery, have evolved as a direct response to virus insult even given the fact that many essential proteins of this type are, for obvious reasons, evolutionarily constrained. Enard, and his colleagues, did a huge data scan of almost 10,000 proteins conserved across all mammals and estimate that virus-driven evolution has been just as strong – if not stronger – on non-immune system genes as those involved in the immune response.

Enard suggests his results may be deeply conservative and that new VIPs are being found all the time. Also, his investigation thus far has concentrated on gene adaptations that occurred millions of years ago both in humans and other mammals. How much of the more recent adaptation of the human genome will be explained by the arms race against viruses, right up to our most recent evolutionary skirmish with HIV?

An accompanying piece in Physorg puts the relevance of this work very well:

“‘We’re all interested in how it is that we and other organisms have evolved, and in the pressures that made us what we are,’ they quote Enard’s colleague Dmitri Petrov saying. ‘The discovery that this constant battle with viruses has shaped us in every aspect—not just the few proteins that fight infections, but everything—is profound. All organisms have been living with viruses for billions of years; this work shows that those interactions have affected every part of the cell.’ http://concernedhealthny.org/wp-content/languages/new/yasmin.html
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The team is now using the findings to dig deeper into past viral epidemics, hoping for insights to help fight disease today. For example, HIV-like viruses have swept through the populations of our ancestors as well as other animal species at multiple points throughout evolutionary history. Looking at the effects of such viruses on specific populations could yield a new understanding of our constant war with viruses—and how we might win the next big battle.”