I Nferences about the Distribution of Dominance Drawn from Yeast 1 Gene Knockout Data 2 3 4

22 Data from several thousand knock-out mutations in yeast (Saccharomyces cerevisiae) 23 were used to estimate the distribution of dominance coefficients. We propose a new 24 unbiased likelihood approach to measuring dominance coefficients. On average, 25 deleterious mutations are partially recessive, with a mean dominance coefficient 26 approximately 0.2. Alleles with large homozygous effects are more likely to be more 27 recessive than are alleles of weaker effect. Our approach allows us to quantify, for the 28 first time, the substantial variance and skew in the distribution of dominance coefficients. 29 This heterogeneity is so great that many population genetic processes analyses based on 30 the mean dominance coefficient alone will be in substantial error. These results are 31 applied to the debate about various mechanisms for the evolution of dominance, and we 32 conclude that they are most consistent with models that depend on indirect selection on 33 homeostatic gene expression or on the ability to perform well under periods of high 34 demand for a protein. 35 __________________________ 36