Environment-independent distribution of mutational effects emerges from microscopic epistasis

A study aimed at uncovering patterns of microscopic and macroscopic epistasis in yeast Saccharomyces cerevisiae in variable environments. Paper abstract draft: Predicting how new mutations alter phenotypes is difficult because mutational effects vary across genotypes and environments. Recent studies found that the effects of many mutations on fitness scale with the fitness of the background genotype, but how the environment modulates this scaling is unknown. We measured the fitness effects of ~100 insertion mutations in 42 strains of Saccharomyces cerevisiae in six laboratory environments. We found that the environment does not alter the background-fitness scaling but tunes one global parameter, the background fitness at which most mutations switch sign. As a result, the distribution of mutational effects is remarkably predictable across genotypes and environments. This apparent simplicity points to some underlying physiological constraints that remain to be discovered.