The Genomic Architecture of Interactions Between Natural Genetic Polymorphisms and Environments in Yeast Growth

Gene-environment interaction (G×E) refers to the phenomenon that the same mutation has different phenotypic effects in different environments. Although quantitative trait loci (QTLs) exhibiting G×E have been reported, little is known about the general properties of G×E, and those of its underlying QTLs. Here, we use the genotypes of 1005 segregants from a cross between two Saccharomyces cerevisiae strains, and the growth rates of these segregants in 47 environments, to identify growth rate QTLs (gQTLs) in each environment, and QTLs that have different growth effects in each pair of environments (g×eQTLs) . The average number of g×eQTLs identified between two environments is 0.58 times the number of unique gQTLs identified in these environments, revealing a high abundance of G×E. Eighty-seven percent of g×eQTLs belong to gQTLs, supporting the practice of identifying g×eQTLs from gQTLs. Most g×eQTLs identified from gQTLs have concordant effects between environments, but, as the effect size of a mutation in one environment enlarges, the probability of antagonism in the other environment increases. Antagonistic g×eQTLs are enriched in dissimilar environments. Relative to gQTLs, g×eQTLs tend to occur at intronic and synonymous sites. The gene ontology (GO) distributions of gQTLs and g×eQTLs are significantly different, as are those of antagonistic and concordant g×eQTLs. Simulations based on the yeast data showed that ignoring G×E causes substantial missing heritability. Together, our findings reveal the genomic architecture of G×E in yeast growth, and demonstrate the importance of G×E in explaining phenotypic variation and missing heritability.