Small effect-size mutations cumulatively affect yeast quantitative traits

Abstract

SummaryQuantitative 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 cumulative play a substantial role in pathway function, potentially by acting as \"modifiers\" that tune the levels of large effect size pathway components. To understand the role of these small effect-size genes, we used a quantitative assay to determine the number, strength, and identity of all non-essential genes that affect two galactose-responsive (GAL) traits, in addition to re-analyzing two previously screened quantitative traits. Over a quarter of assayed genes have a detectable effect; approximately two thirds of the quantitative trait variation comes from small effect-size genes. The functions of small effect-size genes are partially overlapping between traits and are enriched in core cellular processes. This implies that genetic variation in one process has the potential to influence behavior or disease in seemingly unconnected processes.\n\nHighlightsO_LIFour yeast quantitative traits are affected by thousands of small effect-size genes.\nC_LIO_LISmall effect-size genes are enriched in core cellular processes\nC_LIO_LIThe effects of these genes are quantitative trait-specific.\nC_LI