Neaderthal genes have helped Homo sapiens in defending against viral infections

From DNA-sequencing studies of intact cells in hominid fossils (combined with geological-dating evidence where the fossil was located), it is now accepted that modern human (Homo sapiens) diverged from Neaderthal (Homo neaderthalensis) ~600,000 years ago. Several studies have also shown there was interbreeding between these two sublines –– one report was an example ~100,000 years ago, and a second finding ~50,000 years ago. The latter hanky-panky episode left detectable “introgressed segments” (IS) of Neanderthal ancestral DNA within the genomes of non-African modern humans. Recent advances in detection of introgression discovered that the majority of genomic segments initially introgressed from Neanderthals into modern humans were rapidly removed by purifying selection (i.e. the fraction of Neanderthal DNA in Homo sapiens genomes rapidly fell from ~10% to the current levels of 2%–3% in modern Asians and Europeans).

This history of interbreeding and purifying selection against IS raises several intriguing questions. First, among the introgressed sequences that were ultimately retained, can one detect which DNA segments persisted by chance (because they were not critical to survival of the recipient subline), and which persisted because of positive selection (i.e. chance of survival improved –– to find food, avoid predators, and/or reproduce)? Second, if any of the IS were indeed driven by positive selection, can one determine which pressures in the environment drove this adaptation?

Recently this lab [see attached paper] had estimated that virus-interacting proteins (VIPs) accounted for ~30% of protein adaptation into the Homo sapiens genome. Because viruses appear to have driven excess amounts of adaptation into the modern human lineage, and because it is plausible that –– when Neanderthals and modern humans interbred –– they also exchanged viruses via direct contact and/or their shared environment, authors [see attached paper] searched for, and found, long DNA segments of Neanderthal ancestry in Homo sapiens genomes that are enriched for genes encoding VIPs. Furthermore, VIPs that interact specifically with RNA viruses are more likely to belong to Neanderthal IS in modern-day Europeans. These findings suggest that retained segments of Neanderthal ancestry might now be used to detect ancient historical epidemics.

DwN

Cell 2o18; 175: 360–371

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