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 determined 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.