Transition from Background Selection to Associative Overdominance Promotes Diversity in Regions of Low Recombination.
Details
Serval ID
serval:BIB_CF1C14A281EC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Transition from Background Selection to Associative Overdominance Promotes Diversity in Regions of Low Recombination.
Journal
Current biology
ISSN
1879-0445 (Electronic)
ISSN-L
0960-9822
Publication state
Published
Issued date
06/01/2020
Peer-reviewed
Oui
Volume
30
Number
1
Pages
101-107.e3
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
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 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 [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.
Keywords
Genetic Variation, Genome, Human, Humans, Models, Genetic, Recombination, Genetic, Selection, Genetic, deleterious variation, linked selection, pseudo-overdominance, recombination
Pubmed
Web of science
Open Access
Yes
Create date
03/01/2020 16:51
Last modification date
20/02/2024 8:17