Environmental robustness of the global yeast genetic interaction network

Genetic interactions are identified when variants in different genes combine to generate an unusual phenotype compared with the expected combined effect of the corresponding individual variants. For example, a synthetic lethal genetic interaction occurs when two mutations, neither of which is lethal on their own, combine to generate a lethal doublemutant phenotype. Although there are millions of possible gene-gene combinations for any eukaryotic cell, only a rare subset of gene pairs will display a genetic interaction. Digenic, or gene-by-gene (GxG), interactions appear to underlie key aspects of biology, including the relationship between genotype and phenotype. Environmental conditions can modulate the phenotype associated with genetic variants, giving rise to gene-by-environment (GxE) interactions, when a single variant phenotype is modified, or gene-by-gene-by-environment (GxGxE) interactions when a genetic interaction is changed.