Simulating the impact of Neandertal introgression on the distribution of fitness effects of human genetic variation

2020-04-20T21:50:17Z (GMT) by Sara Carioscia Rajiv Mccoy
Understanding how natural selection has shaped the fitness effects of standing genetic variation is a major goal of evolutionary genetics. Hominin admixture offers a useful model for considering this question, given the hypothesized differences in population size between modern and archaic humans. Specifically, studies have suggested that Neandertal populations accumulated a load of weakly deleterious mutations due to the small populations resulting from prolonged demographic bottlenecks. We thus investigated how introgression from these archaic hominins contributes to the distribution of fitness effects of contemporary human genetics.

To look at this, we develop an evolutionary simulation using the software SLiM, building on published models of human demographic history. At the end of our simulation, we consider the mutations that persisted into the present-day Eurasian population. These mutations could have originated in the ancestral or African population, in the small Neandertal population and then introgressed in, or in the Eurasian population itself. To examine how the different evolutionary histories of each population influenced which mutations were able to persist, we compare the selection coefficients of each mutation.


We found that Neandertal-originating mutations were modestly enriched for deleterious effects compared to a background of modern human variation of similar age, reflecting the impact of genetic drift in the small Neandertal population. Rare, recent mutations originating in modern humans were also enriched for deleterious effects compared to frequency matched archaic variation. The effects of these recent mutations are the most significant contributor to deleterious effects in the final population, outweighing the effects of this long divergence time and the strong drift in the Neandertal population.

Our findings demonstrate that rare, recent mutations make an outsize contribution to deleterious fitness effects of segregating human variation, corroborating recent work suggesting that these mutations contribute significantly to the heritability of complex traits. This conclusion also suggests that some trait associations previously attributed to archaic admixture may be driven by recent, rare modern mutations that segregate in linkage disequilibrium with archaic haplotypes. Our findings provide a theoretical foundation for studies of the functional and fitness impacts of archaic introgression and comparisons with mutations of modern human origin.