FIG 1.

Different types of epistasis between two loci defining the fitness of a genotype. ○, wild-type allele; ●, mutant allele. (a) In the case of no epistasis, the fitness of the double mutant (●●) results from multiplying the fitness effects of both mutations in the wild-type genetic background (i.e., the fitness levels for genotypes ●○ and ○●). (b) If magnitude epistasis exists, the fitness of the double mutant (●●) is different from the multiplicative expectation. In the example, the observed fitness of ●● is larger than expected as a consequence of positive epistasis. In the cases of both no epistasis and magnitude epistasis, the effects of mutations ●○ and ○● are unconditionally beneficial. (c) If the effect of one of the mutations is conditionally beneficial (i.e., beneficial in one genetic background but deleterious in another), then we have the situation of sign epistasis. (d) Finally, if both mutations ●○ and ○● are deleterious by themselves but beneficial when combined, we have the situation of reciprocal sign epistasis.