%0 Journal Article %1 gilbert2019transition %A Gilbert, Kimberly J. %A Pouyet, Fanny %A Excoffier, Laurent %A Peischl, Stephan %D 2019 %I Cold Spring Harbor Laboratory %J bioRxiv %K background_selection genetic_load heterozygote_advantage population_genetics %R 10.1101/748004 %T Transition from background selection to associative overdominance promotes diversity in regions of low recombination %U https://www.biorxiv.org/content/early/2019/08/28/748004 %X Linked selection is a major driver of genetic diversity. Selection against deleterious mutations removes linked neutral diversity (background selection, BGS, Charlesworth et al. 1993), creating a positive correlation between recombination rates and genetic diversity. Purifying selection against recessive variants, however, can also lead to associative overdominance (AOD, Ohta 1971, Zhao & Charlesworth, 2016), due to an apparent heterozygote advantage at linked neutral loci that opposes the loss of neutral diversity by BGS. Zhao & Charlesworth (2016) identified the conditions when 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 co-segregate. 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 (Ohta & Kimura 1970), 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 (Pouyet et al. 2018), the observation of a resurgence of genetic diversity in regions of very low recombination is indicative of AOD. We identify 21 such regions in the human genome showing clear signals of multi-locus AOD. Our results demonstrate that AOD may play an important role in the evolution of low recombination regions of many species.

@article{gilbert2019transition, abstract = {Linked selection is a major driver of genetic diversity. Selection against deleterious mutations removes linked neutral diversity (background selection, BGS, Charlesworth et al. 1993), creating a positive correlation between recombination rates and genetic diversity. Purifying selection against recessive variants, however, can also lead to associative overdominance (AOD, Ohta 1971, Zhao \& Charlesworth, 2016), due to an apparent heterozygote advantage at linked neutral loci that opposes the loss of neutral diversity by BGS. Zhao \& Charlesworth (2016) identified the conditions when 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 co-segregate. 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 (Ohta \& Kimura 1970), 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 (Pouyet et al. 2018), the observation of a resurgence of genetic diversity in regions of very low recombination is indicative of AOD. We identify 21 such regions in the human genome showing clear signals of multi-locus AOD. Our results demonstrate that AOD may play an important role in the evolution of low recombination regions of many species.}, added-at = {2019-09-03T23:18:21.000+0200}, author = {Gilbert, Kimberly J. and Pouyet, Fanny and Excoffier, Laurent and Peischl, Stephan}, biburl = {https://www.bibsonomy.org/bibtex/2c1af6ff709c5ff83f0ce4dd306c974f3/peter.ralph}, doi = {10.1101/748004}, elocation-id = {748004}, eprint = {https://www.biorxiv.org/content/early/2019/08/28/748004.full.pdf}, interhash = {8273b15c8789acc3c47061d3d37f7ef9}, intrahash = {c1af6ff709c5ff83f0ce4dd306c974f3}, journal = {bioRxiv}, keywords = {background_selection genetic_load heterozygote_advantage population_genetics}, publisher = {Cold Spring Harbor Laboratory}, timestamp = {2019-09-03T23:18:21.000+0200}, title = {Transition from background selection to associative overdominance promotes diversity in regions of low recombination}, url = {https://www.biorxiv.org/content/early/2019/08/28/748004}, year = 2019 }