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.
%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
}