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MathBio Seminar

Monday, February 15, 2016 - 4:00pm

Kelley Harris

Stanford University


University of Pennsylvania

318 Carolyn Lynch Lab

In human populations living outside Africa, at least 2-4% of the gene pool is inferred to have Neanderthal origin. This is the result of interbreeding between humans and Neanderthals that took place soon after humans first migrated out of Africa. Recent studies have shown that this Neanderthal DNA appears to be most abundant in regions of the genome that have no known functional importance, whereas Neanderthal DNA appears to be depleted from regions of the human genome that are subject to strong evolutionary constraint. A possible explanation for this pattern is that early human-Neanderthal hybrids had low fertility or fitness due to epistatic incompatibilities between the two species. In this talk I will present a possible alternative explanation: that Neanderthals had lower fitness than their human contemporaries due to long periods of inbreeding and low population size. Using published estimates of Neanderthal effective population size history and the distribution of mutational fitness effects, we infer that Neanderthal fitness was at least 40% lower than human fitness on average. This mutational load implies that Neanderthal DNA should have been selected against and depleted from functional regions of the genome without need to invoke epistasis. We also predict a residual Neanderthal mutation load in non-Africans, leading to a fitness reduction of at least 0.5%. This effect of Neanderthal admixture has been left out of previous debate on mutation load differences between Africans and non-Africans. We also show that if many deleterious mutations are recessive, the Neanderthal admixture fraction could increase over time due to the protective effect of Neanderthal haplotypes against deleterious alleles that arose recently in the human population. This might partially explain why so many organisms retain gene flow from other species and appear to derive adaptive benefits from introgression. This is joint work with Rasmus Nielsen.