Multi-locus Genotypes Underlying Temperature Sensitivity in a Mutationally Induced Trait

Determining how genetic variation alters the expression of heritable phenotypes across conditions is important for agriculture, evolution, and medicine. Central to this problem is the concept of genotype-by-environment interaction (or ‘GxE’), which occurs when segregating genetic variation causes individuals to show different phenotypic responses to the environment. While many studies have sought to identify individual loci that contribute to GxE, obtaining a deeper understanding of this phenomenon may require defining how sets of loci collectively alter the relationship between genotype, environment, and phenotype. Here, we identify combinations of alleles at seven loci that control how a mutationally induced colony phenotype is expressed across a range of temperatures (21, 30, and 37°C) in a panel of yeast recombinants. We show that five predominant multi-locus genotypes involving the detected loci result in trait expression with varying degrees of temperature sensitivity. By comparing these genotypes and their patterns of trait expression across temperatures, we demonstrate that the involved alleles contribute to temperature sensitivity in different ways. While alleles of the transcription factor MSS11 specify the potential temperatures at which the trait can occur, alleles at the other loci modify temperature sensitivity within the range established by MSS11 in a genetic background- and/or temperature-dependent manner. Our results not only represent one of the first characterizations of GxE at the resolution of multi-locus genotypes, but also provide an example of the different roles that genetic variants can play in altering trait expression across conditions.