Resolving the conflict between associative overdominance and background selection

In small populations, genetic linkage between a polymorphic neutral locus and loci subject to selection, either against partially recessive mutations or in favor of heterozygotes, may result in an apparent selective advantage to heterozygotes at the neutral locus (associative overdominance), and a retardation of the rate of loss of variability by genetic drift at this locus. In large populations, selection against deleterious mutations has previously been shown to reduce variability at linked neutral loci (background selection). We describe analytical, numerical and simulation studies that shed light on the conditions under which retardation versus acceleration of loss of variability occurs at a neutral locus linked to a locus under selection. We consider a finite, randomly mating population initiated from an infinite population in equilibrium at a locus under selection, with no linkage disequilibrium. With mutation and selection, retardation only occurs when S, the product of twice the effective population size and the selection coefficient, is of order one. With S >> 1, background selection always causes an acceleration of loss of variability. Apparent heterozygote advantage at the neutral locus is, however, always observed when mutations are partially recessive, even if there is an accelerated rate of loss of variability. With heterozygote advantage at the selected locus, there is nearly always a retardation of loss of variability. The results shed light on experiments on the loss of variability at marker loci in laboratory populations, and on the results of computer simulations of the effects of multiple selected loci on neutral variability.