Epistatic interactions of spontaneous mutations in haploid strains of the yeast Saccharomyces cerevisiae

Several important biological phenomena, including genetic recombination and sexual reproduction, could have evolved to counteract genome contamination by deleterious mutations. This postulate would be especially relevant if it were shown that deleterious mutations interact in such a way that their individual negative effects are reinforced by each other. The hypothesis of synergism can be tested experimentally by crossing organisms bearing deleterious mutations and comparing the fitness of the parents and their progeny. The present study used laboratory strains of the budding yeast burdened with mutations resulting from absence of a major DNA mismatch repair function. Only in one, or possibly two, crosses out of eight did fitness of the progeny deviate from that of their parents in a direction indicating synergism. Furthermore, the distributions of progeny fitness were not skewed as would be expected if strong interactions were present. The choice of experimental material ensured that genetic recombination was extensive, all four meiotic products were available for fitness assays, and that the mutations were probably numerous. Despite this generally favourable experimental setting, synergism did not appear to be a dominating force shaping fitness of yeast containing randomly generated mutations.