THE EFFECT OF DELETERIOUS MUTATIONS ON NEUTRAL MOLECULAR VARIATION

Selection against deleterious alleles maintained by mutation may cause a reduction in the amount of genetic variability at linked neutral si tes. 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 th at are free of deleterious alleles, and hence are not destined for rap id 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 div ersity, and number of segregating sites. These formulas apply to rando m-mating populations with no genetic recombination, and to populations reproducing exclusively asexually or by self-fertilization. For a giv en 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 decre ases rapidly with increasing recombination frequency or rate of outcro ssing. The mean time to loss of new neutral mutations and the total nu mber of segregating neutral sites are less sensitive to background sel ection than the other statistics, unless the population size is of the order of a hundred thousand or more. The stationary distribution of a llele frequencies at the neutral sites is correspondingly skewed in fa vor of rare alleles, compared with the classical neutral result. Obser ved reductions in molecular variation in low recombination genomic reg ions of sufficiently large size, for instance in the centromere-proxim al regions of Drosophila autosomes or in highly selfing plant populati ons, may be partly due to background selection against deleterious mut ations.