In “The Causes of Evolution” published in 1932, Haldane formulated the hypothesis that pathogens are a major driver of hosts' evolution. Adaptation against pathogens has since then been studied mostly in genes specialized in the immune response.
Yet pathogens, and in particular viruses, interact with hundreds to thousands of host proteins that are not specialized in the immune response. Whether adaptation to viruses has typically involved only specialized immune, antiviral proteins or has affected a broad array of proteins is unknown. Here, we analyze patterns of adaptation in thousands of virus-interacting proteins at different evolutionary time scales ranging from the whole mammalian phylogenetic tree to the past 10,000 years of human evolution.
Over long evolutionary time scales, we find that virus-interacting proteins have experienced strongly increased rates of adaptation across the entire mammalian phylogeny, from primates to rodents to bats and elephants. In the human branch, we estimate that 30% of all adaptive protein changes since divergence with chimpanzees were driven by viruses.
During recent human evolution, we find that virus-interacting proteins exhibit a very strong excess of partial and complete sweeps. Importantly, recent human adaptation against viruses is driven not only by immune proteins but instead by proteins from a wide range of host cellular functions.
Our results show that the influence of pathogens extends well beyond the classic cases of specialized immune proteins, and that pathogens are a major driver of adaptation at the whole genome level.