Gene interactions that make fitness non-additive across loci
Epistasis occurs when the effect of a mutation at one locus depends on the genetic background (other loci).
Positive epistasis: double mutant is fitter than expected additively.
Sign epistasis: a beneficial mutation becomes deleterious in a different background — creates local fitness peaks and limits evolutionary paths.
Reciprocal sign epistasis is necessary for multiple fitness peaks (rugged landscapes).