Epistatic interactions between mutations are widespread. Theoretical investigations have shown that variability in epistatic effects influences fundamental evolutionary processes, yet few empirical studies have identified causes or the extent of this variation. We examined variation in epistatic effects of mutations at two host recognition sites in φX174 bacteriophage. We calculated epistatic effects from the sum of fitness effects (log scale) of two single mutants and their corresponding double mutant for five combinations of mutations in six conditions. We found that epistatic effects differed in sign, degree, and variability across conditions. The data highlight that even between single mutations at the same two sites the sign and variability of epistatic effects are affected by environment. We discuss these findings in the context of studying the role of epistasis in evolution.
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