A bulk barcoded quantitative trait locus approach increases the power and resolution of genotype-phenotype mapping in yeast, revealing that the genetic architecture of 18 complex traits is highly polygenic, and is characterized by widespread epistatic interactions and pleiotropic effects.

A complete mutational scan of a protein-DNA interface shows that pairwise epistatic interactions among amino acids determine a transcription factor's specificity for DNA and facilitate the evolution of new functions.

Monosomy in yeast results in numerous gene dosage insufficiencies with potentially lethal collective effect, but strong positive epistasis rooted in the modular structure of cell metabolism cancels it.

Many of the synergistic interactions between mutations are modified in the context of unstable proteins in a manner that depends on how the variants promote misfolding in the cell.

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.

Predictable patterns of fitness evolution observed in microbial evolution experiments can emerge generically as a consequence of widespread epistatic interactions between mutations.

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.

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

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

Multiple replicated examples of epistasis affecting gene expression in humans are identified, some explaining a substantial proportion of the variation in expression.