Influence of dominance, leptokurtosis and pleiotropy of deleterious mutations on quantitative genetic variation at mutation-selection balance

In models of maintenance of genetic variance (V-G) it has often been assumed that mutant alleles act additively. However, experimental data show that the dominance coefficient varies among mutant alleles and those of large effect tend to be recessive. On the basis of empirical knowledge of mutations, a joint-effect model of pleiotropic and real stabilizing selection that includes dominance is constructed and analyzed. It is shown that dominance can dramatically alter the prediction of equilibrium V-G. Analysis indicates that for the situations where mutations are more recessible for fitness than for a quantitative trait, as supported by the available data, the joint-effect model predicts a significantly higher V-G than does an additive model. Importantly, for what seem to be realistic distributions of mutational effects (i.e., many mutants may not affect the quantitative trait substantially but are likely to affect fitness), the observed high levels of genetic variation in the quantitative trait under strong apparent stabilising selection can be generated. This investigation supports the hypothesis that most V-G come from the alleles nearly neutral for fitness in heterozygotes while apparent stabilising selection is contributed mainly by the alleles of large effect on the quantitative trait. Thus considerations of dominance coefficients of mutations lend further support to our previous conclusion that mutation-selection balance is a plausible mechanism of the maintenance of the genetic variance in natural populations.