Viruses are a dominant driver of protein adaptation in mammals

David Enard, Le Cai, Carina Gwennap, Dmitri A. Petrov

Research output: Contribution to journalArticlepeer-review

188 Scopus citations


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.

Original languageEnglish (US)
Article numbere12469
StatePublished - May 17 2016


  • adaptive evolution
  • computational biology
  • evolutionary biology
  • genomics
  • host/pathogen interactions
  • human
  • human evolution
  • mammals
  • systems biology
  • viruses

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology
  • General Neuroscience


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