Evidence that RNA Viruses Drove Adaptive Introgression between Neanderthals and Modern Humans

Neanderthals and modern humans interbred at least twice in the past 100,000 years. While there is evidence that most introgressed DNA segments from Neanderthals to modern humans were removed by purifying selection, less is known about the adaptive nature of introgressed sequences that were retained. We hypothesized that interbreeding between Neanderthals and modern humans led to (1) the exposure of each species to novel viruses and (2) the exchange of adaptive alleles that provided resistance against these viruses. Here, we find that long, frequent—and more likely adaptive—segments of Neanderthal ancestry in modern humans are enriched for proteins that interact with viruses (VIPs). We found that VIPs that interact specifically with RNA viruses were more likely to belong to introgressed segments in modern Europeans. Our results show that retained segments of Neanderthal ancestry can be used to detect ancient epidemics. Human genome evolution after Neanderthal interbreeding was shaped by viral infections and the resulting selection for ancient alleles of viral-interacting protein genes.