Inferences about the distribution of dominance drawn from yeast gene knockout data

Data from several thousand knockout mutations in yeast (Saccharomyces cerevisiae) were used to estimate the distribution of dominance coefficients. We propose a new unbiased likelihood approach to measuring dominance coefficients. On average, deleterious mutations are partially recessive, with a mean dominance coefficient ~0.2. Alleles with large homozygous effects are more likely to be more recessive than are alleles of weaker effect. Our approach allows us to quantify, for the first time, the substantial variance and skew in the distribution of dominance coefficients. This heterogeneity is so great that many population genetic processes analyses based on the mean dominance coefficient alone will be in substantial error. These results are applied to the debate about various mechanisms for the evolution of dominance, and we conclude that they are most consistent with models that depend on indirect selection on homeostatic gene expression or on the ability to perform well under periods of high demand for a protein.