Abstract:

Cryptic genetic variants that do not typically influence traits can interact with each other, the environment, and mutations to cause unexpected phenotypes. The genetic architectures and molecular mechanisms that underlie these interactions are not well understood. To help advance knowledge in this area, we comprehensively dissected the genetic basis of a cryptic yeast colony trait across multiple mutant backgrounds and environments in a yeast cross. Across our studies, we identified 12 specific genes and 6 uncharacterized loci that harbor cryptic variants, as well as 7 ‘capacitor’ genes that can reveal these cryptic variants when mutated. Additionally, we defined specific, complex combinations of epistatically interacting cryptic variants that can lead to the colony phenotype in particular mutant backgrounds or environments. Most of the identified capacitors and genes harboring cryptic variants act in the evolutionarily conserved and oncogenic Ras signaling cascade, and appear to influence the activities of antagonistic, Ras-regulated transcription factors. Thus, our results suggest that complicated genetic and environmental influences on gene regulatory networks play a key role in suppressing and uncovering cryptic phenotypes.