The role of population size in molecular evolution

The results of a computer simulation study of the role of population size in population genetical models of molecular evolution are presented. If the mutation rate and strength of selection are held fixed and the population size increased, the eight models examined fall into three domains based on their rates of substitution. In the Ohta domain, the rate of substitution decreases 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 domains, 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 neutral locus linked to a selected locus is found to be insensitive to the population size for certain models of selection. A selected locus can actually cause the rate of substitution of deleterious alleles at a linked locus to increase with increasing population size. These unexpected results illustrate that intuition based on two-allele theory is often misleading.