Epistasis

Dependence of the effect of one genetic change on another. Double-mutant and bypass experiments can order functional requirements, but phenotype suppression alone does not prove a direct molecular interaction.

Testing whether forced activity of a downstream candidate restores an output after another gene is impaired. Rescue supports functional sufficiency in the tested context, but parallel routes and overexpression can also bypass a defect.

An interaction in which the sign of a genetic change’s fitness effect depends on the genetic background. It constrains which steps increase fitness along an adaptive walk.