Transition from Background Selection to Associative Overdominance Promotes Diversity in Regions of Low Recombination

Gilbert, Kimberly J.; Pouyet, Fanny; Excoffier, Laurent; Peischl, Stephan (2020). Transition from Background Selection to Associative Overdominance Promotes Diversity in Regions of Low Recombination. Current Biology, 30(1), pp. 101-107. Cell Press 10.1016/j.cub.2019.11.063

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Linked selection is a major driver of genetic diversity. Selection against deleterious mutations removes linked neutral diversity (background selection [BGS]) [1], creating a positive correlation between recombination rates and genetic diversity. Purifying selection against recessive variants, however, can also lead to associative overdominance (AOD) [2, 3], due to an apparent heterozygote advantage at linked neutral loci that opposes the loss of neutral diversity by BGS. Zhao and Charlesworth [3] identified the conditions under which AOD should dominate over BGS in a single-locus model and suggested that the effect of AOD could become stronger if multiple linked deleterious variants cosegregate. We present a model describing how and under which conditions multi-locus dynamics can amplify the effects of AOD.We derive the conditions for a transition from BGS to AOD due to
pseudo-overdominance [4], i.e., a form of balancing selection that maintains complementary deleterious haplotypes that mask the effect of recessive deleterious mutations. Simulations confirm these findings and show that multi-locus AOD can increase diversity in low-recombination regions much more strongly than previously appreciated. While BGS is known to drive genome-wide diversity in humans [5], the observation of a resurgence of genetic diversity in regions of very low recombination is indicative of AOD. We identify 22 such regions in the human genome consistent with multi-locus AOD. Our results demonstrate that AOD may play an important role in the evolution of low-recombination regions of many species.

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