Transcriptional derepression uncovers cryptic higher-order genetic interactions. Saccharomyces cerevisiae

Some genetic polymorphisms have phenotypic effects that are masked under most conditions, but can be uncovered by mutations or environmental change. Because these cryptic variants might contribute to heritable phenotypic variation, including novel traits and heritable diseases, it is important to understand their extent within populations, as well as the mechanisms that suppress and uncover them. Here, we use a model of cryptic variation in budding yeast to address these problems. We show that a single mutation in a yeast cross reveals six cryptic variants that genetically interact in two combinations. The mutation uncovers these cryptic variants by disrupting the transcriptional repression of one or more genes that must be expressed for the cryptic variants to exert their effects.