Of Neanderthals and Denisovans, and how they live on in many of us.

I will describe our work to sequence genomes from Neandertals as well as a previously unknown extinct Asian hominin group related to Neandertals, which we named “Denisovans”. Analyses of these genomes show that gene flow occurred among modern human ancestors and these archaic hominins. As a consequence, about 2.0% of the genomes of people living outside Africa come from Neandertals while about 5.0% of the genomes of people living in Oceania come from Denisovans. These genetic contributions have numerous physiological and medical consequences today. I will describe some such changes that influence sensitivity to pain and to infections. I will also describe some changes that appeared and rose to high frequencies in modern humans since their divergence from a common ancestor shared with the archaic hominins, for example an amino acid substitution in the enzyme ADSL that affect purine biosynthesis, particularly in the brain, and behavior in a mouse model and in humans. I will suggest that the genetic basis of the modern human phenotype is likely to be a combination of several or many genetic features, where not every feature is present in every present-day human.