The role of population size in molecular evolution

The results of a computer simulation study of the role of population size i n population genetical models of molecular evolution are presented. If the mutation rate and strength of selection are held fixed and the population s ize increased, the eight models examined fall into three domains based on t heir rates of substitution. In the Ohta domain, the rate of substitution de creases with increasing population size; in the Kimura domain, the rate of substitution remains close to the mutation rate; in the Darwin domain, the rate of substitution increases without bound. In the Kimura and Darwin doma ins, the rate of substitution is much less sensitive to the population size than suggested by two-allele theories, Remarkably, the overdominance model converges to the neutral model with increasing N. The variation at a neutr al locus linked to a selected locus is found to be insensitive to the popul ation size for certain models of selection. A selected locus can actually c ause the rate of substitution of deleterious alleles at a linked locus to i ncrease with increasing population size. These unexpected results illustrat e that intuition based on two-allele theory is often misleading. (C) 1999 A cademic Press.