TY - JOUR
T1 - Background Selection From Unlinked Sites Causes Nonindependent Evolution of Deleterious Mutations
AU - Matheson, Joseph
AU - Masel, Joanna
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/3/1
Y1 - 2024/3/1
N2 - Background selection describes the reduction in neutral diversity caused by selection against deleterious alleles at other loci. It is typically assumed that the purging of deleterious alleles affects linked neutral variants, and indeed simulations typically only treat a genomic window. However, background selection at unlinked loci also depresses neutral diversity. In agreement with previous analytical approximations, in our simulations of a human-like genome with a realistically high genome-wide deleterious mutation rate, the effects of unlinked background selection exceed those of linked background selection. Background selection reduces neutral genetic diversity by a factor that is independent of census population size. Outside of genic regions, the strength of background selection increases with the mean selection coefficient, contradicting the linked theory but in agreement with the unlinked theory. Neutral diversity within genic regions is fairly independent of the strength of selection. Deleterious genetic load among haploid individuals is underdispersed, indicating nonindependent evolution of deleterious mutations. Empirical evidence for underdispersion was previously interpreted as evidence for global epistasis, but we recover it from a non-epistatic model.
AB - Background selection describes the reduction in neutral diversity caused by selection against deleterious alleles at other loci. It is typically assumed that the purging of deleterious alleles affects linked neutral variants, and indeed simulations typically only treat a genomic window. However, background selection at unlinked loci also depresses neutral diversity. In agreement with previous analytical approximations, in our simulations of a human-like genome with a realistically high genome-wide deleterious mutation rate, the effects of unlinked background selection exceed those of linked background selection. Background selection reduces neutral genetic diversity by a factor that is independent of census population size. Outside of genic regions, the strength of background selection increases with the mean selection coefficient, contradicting the linked theory but in agreement with the unlinked theory. Neutral diversity within genic regions is fairly independent of the strength of selection. Deleterious genetic load among haploid individuals is underdispersed, indicating nonindependent evolution of deleterious mutations. Empirical evidence for underdispersion was previously interpreted as evidence for global epistasis, but we recover it from a non-epistatic model.
KW - effective population size
KW - expected heterozygosity
KW - forward-time simulation
KW - linkage disequilibrium
KW - nearly neutral theory
KW - population genetics
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U2 - 10.1093/gbe/evae050
DO - 10.1093/gbe/evae050
M3 - Article
C2 - 38482769
AN - SCOPUS:85189374887
SN - 1759-6653
VL - 16
JO - Genome biology and evolution
JF - Genome biology and evolution
IS - 3
M1 - evae050
ER -