Widespread Cumulative Influence of Small Effect Size Mutations on Yeast Quantitative Traits

Quantitative traits are influenced by pathways that have traditionally been defined through genes that have a large loss- or gain-of-function effect. However, in theory, a large number of small effect size genes could cumulatively play a substantial role in pathway function. Here, we determine the number, strength, and identity of all non-essential test genes that affect two quantitative galactose-responsive traits in addition to re-analyzing two previously screened quantitative traits. We find that over a quarter of assayed genes have a detectable, quantitative effect on phenotype. Despite their ubiquity, these genes are enriched in core cellular processes in a trait-specific manner. In a simulated population with 50% frequency of all-or-none alleles, we show that small effect size alleles are capable of contributing more to trait variation than alleles in a canonical, large effect size pathway. In total, by demonstrating that the genes effecting quantitative traits can be highly distributed and interconnected, this work challenges the concept of pathways as modular and independent.