Viruses are a dominant driver of protein adaptation in mammals
David Enard Le Cai Carina Gwennap Dmitri A Petrov
Stanford University, United States
Published May 17, 2016
Cite as eLife 2016;5:e12469
Viruses interact with hundreds to thousands of proteins in mammals, yet adaptation against viruses has only been studied in a few proteins specialized in antiviral defense. Whether adaptation to viruses typically involves only specialized antiviral proteins or affects a broad array of virus-interacting proteins is unknown. Here, we analyze adaptation in ~1300 virus-interacting proteins manually curated from a set of 9900 proteins conserved in all sequenced mammalian genomes. We show that viruses (i) use the more evolutionarily constrained proteins within the cellular functions they interact with and that (ii) despite this high constraint, virus-interacting proteins account for a high proportion of all protein adaptation in humans and other mammals. Adaptation is elevated in virus-interacting proteins across all functional categories, including both immune and non-immune functions. We conservatively estimate that viruses have driven close to 30% of all adaptive amino acid changes in the part of the human proteome conserved within mammals. Our results suggest that viruses are one of the most dominant drivers of evolutionary change across mammalian and human proteomes.
When an environmental change occurs, species are able to adapt in response due to mutations in their DNA. Although these mutations occur randomly, by chance some of them make the organism better suited to their new environment. These are known as adaptive mutations.
In the past ten years, evolutionary biologists have discovered a large number of adaptive mutations in a wide variety of locations in the genome – the complete set of DNA – of humans and other mammals. The fact that adaptive mutations are so pervasive is puzzling. What kind of environmental pressure could possibly drive so much adaptation in so many parts of the genome?
Viruses are ideal suspects since they are always present, ever-changing and interact with many different locations of the genome. However, only a few mammalian genes had been studied to see whether they adapt to the presence of viruses. By studying thousands of proteins whose genetic sequence is conserved in all mammalian species, Enard et al. now suggest that viruses explain a substantial part of the total adaptation observed in the genomes of humans and other mammals. For instance, as much as one third of the adaptive mutations that affect human proteins seem to have occurred in response to viruses.
So far, Enard et al. have only studied old adaptations that occurred millions of years ago in humans and other mammals. Further studies will investigate how much of the recent adaptation in the human genome can also be explained by the arms race against viruses.
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