The effect of deleterious mutations on neutral molecular variation.
Genetics, 134 (4):
1289--1303 (August 1993)Abstract
Selection against deleterious alleles maintained by mutation may cause a reduction in the amount
of genetic variability at linked neutral sites. This is because a new neutral variant can only remain in
a large population for a long period of time if it is maintained in gametes that are free of deleterious
alleles, and hence are not destined for rapid elimination from the population by selection. Approximate
formulas are derived for the reduction below classical neutral values resulting from such background
selection against deleterious mutations, for the mean times to fixation and loss of new mutations,
nucleotide site diversity, and number of segregating sites. These formulas apply to random-mating
populations with no genetic recombination, and to populations reproducing exclusively asexually or
by self-fertilization. For a given selection regime and mating system, the reduction is an exponential
function of the total mutation rate to deleterious mutations for the section of the genome involved.
Simulations show that the effect decreases rapidly with increasing recombination frequency or rate of
outcrossing. The mean time to loss of new neutral mutations and the total number of segregating
neutral sites are less sensitive to background selection than the other statistics, unless the population
size is of the order of a hundred thousand or more. The stationary distribution of allele frequencies
at the neutral sites is correspondingly skewed in favor of rare alleles, compared with the classical
neutral result. Observed reductions in molecular variation in low recombination genomic regions of
sufficiently large size, for instance in the centromere-proximal regions of Drosophila autosomes or in
highly selfing plant populations, may be partly due to background selection against deleterious
mutations.