Epistatic buffering of fitness loss in yeast double deletion strains

Interactions between deleterious mutations have been insufficiently studied(1,2), despite the fact that their strength and direction are critical for understanding the evolution of genetic recombination(3,4) and the buildup of mutational load in populations(5,6). We compiled a list of 758 yeast gene deletions causing growth defects ( from the Munich Information Center for Protein Sequences database and ref. 7). Using BY4741 and BY4742 single- deletion strains, we carried out 639 random crosses and assayed growth curves of the resulting progeny. We show that the maximum growth rate averaged over strains lacking deletions and those with double deletions is higher than that of strains with single deletions, indicating a positive epistatic effect. This tendency is shared by genes belonging to a variety of functional classes. Based on our data and former theoretical work(8-10), we suggest that epistasis is likely to diminish the negative effects of mutations when the ability to produce biomass at high rates contributes significantly to fitness.