Environment Determines Epistatic Patterns for a ssDNA Virus

Despite the accumulation of substantial quantities of information about epistatic interactions among both deleterious and beneficial mutations in a wide array of experimental systems, neither consistent patterns nor causal explanations for these interactions have yet emerged. Furthermore, the effects of mutations depend on the environment in which they are characterized, implying that the environment may also influence epistatic interactions. Recent work with beneficial mutations for the single-stranded DNA bacteriophage ID11 demonstrated that interactions between pairs of mutations could be understood by means of a simple model that assumes that mutations have additive phenotypic effects and that epistasis arises through a nonlinear phenotype–fitness map with a single intermediate optimum. To determine whether such a model could also explain changes in epistatic patterns associated with changes in environment, we measured epistatic interactions for these same mutations under conditions for which we expected to find the wild-type ID11 at different distances from its phenotypic optimum by assaying fitnesses at three different temperatures: 33°, 37°, and 41°. Epistasis was present and negative under all conditions, but became more pronounced as temperature increased. We found that the additive-phenotypes model explained these patterns as changes in the parameters of the phenotype–fitness map, but that a model that additionally allows the phenotypes to vary across temperatures performed significantly better. Our results show that ostensibly complex patterns of fitness effects and epistasis across environments can be explained by assuming a simple structure for the genotype–phenotype relationship.