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.
Pairwise combinations of growth-promoting genes regulating distinct cellular mechanisms lead to synergistic effects on leaf growth, and hence greatly increased leaf size.
Variable petal number in Cardamine hirsuta is explained by regulatory changes in the MADS-box gene APETALA1 that relaxed its epistasis over mapped QTL in the C. hirsuta genome.
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.
Multiple replicated examples of epistasis affecting gene expression in humans are identified, some explaining a substantial proportion of the variation in expression.
Deletion of one gene can lead to inactivation of other genes which restore a perturbed cellular function but change the epistatic interactions and the dynamics of the responsible module.
