Thermodynamic framework accurately predicts the sign of epistasis and its environment dependence for a canonical cis-regulatory element.

Drug resistance in HIV is the result of mutations, which affect fitness depending on epistatic interactions with the entire sequence background that varies within and between patient populations.

Experimental mapping of the joint sequence space of an ancient transcription factor (TF) and its DNA binding sites reveals that epistasis across the molecular interface permitted the evolution of a new and specific TF-DNA complex.

Greater phenotypic variation is exposed by mutations in a gene regulatory system compared to mutations in its constitutive components, namely the transcription factor and the promoter, alone.

Some of the mutations that occur during influenza evolution can only be tolerated in conjunction with other mutations that increase the stability of a viral protein.

Genome engineering and phenotyping in vivo reveal surprising new features of adaptive amino acid substitutions that were previously inaccessible.

Pairwise combinations of growth-promoting genes regulating distinct cellular mechanisms lead to synergistic effects on leaf growth, and hence greatly increased leaf size.

Rectangular order perturbations generalize sign epistasis, capture global aspects of fitness landscapes, and clarify how rank order approaches relate.

The epistasis observed in TF-DNA binding preferences can be explained by the presence of two optima of very similar Gibbs energy that are located relatively far from each other in sequence space.