Viruses rule over adaptation in conserved human proteins

Adaptive evolution often involves fast-evolving proteins, and the fastest-evolving proteins in primates include antiviral proteins engaged in an arms race with viruses 1-3. Even though fast-evolving antiviral proteins are the most studied cases of primate host adaptation against viruses, viruses predominantly interact with host proteins that are broadly conserved between distant species in order to complete their replication cycle 4. Broadly conserved proteins are generally viewed as playing a negligible role in adaptive evolution. Here, we used a dataset of ~4,500 human proteins known to physically interact with viruses (VIPs for Virus-Interacting Proteins), to test the involvement of broadly conserved proteins in adaptive evolution against viruses. We found that VIPs conserved between animals and fungi have experienced not only high rates of adaption, but also strong adaptive events. Broadly conserved proteins that do not interact with viruses experienced very little adaptation. As a result, the arms race with viruses explains more than 75% of adaptation in the most phylogenetically conserved subset of the human proteome. Our results imply that broadly conserved proteins have played a significant role in adaptation, and that viruses were likely one of very few selective pressures that were able to force the conserved, central pillars of host cellular functions to adapt during evolution.