The distribution of epistasis on simple fitness landscapes

Fitness interactions between mutations can influence a population’s evolution in many different ways. While epistatic effects are difficult to measure precisely, important information about the overall distribution is captured by the mean and variance of log fitnesses for individuals carrying different numbers of mutations. We derive predictions for these quantities from simple fitness landscapes, based on models of optimizing selection on quantitative traits. We also explore extensions to the models, including modular pleiotropy, variable effects sizes, mutational bias, and maladaptation of the wild-type. We illustrate our approach by reanalysing a large data set of mutant effects in a yeast snoRNA. Though characterized by some strong epistatic interactions, these data give a good overall fit to the non-epistatic null model, suggesting that epistasis might have little effect on the evolutionary dynamics in this system. We also show how the amount of epistasis depends on both the underlying fitness landscape, and the distribution of mutations, and so it is expected to vary in consistent ways between new mutations, standing variation, and fixed mutations.