Edge CMT: identifying genes that shape complex multigenic traits within and between yeast species - most phenotypic traits, including nearly all morphological, physiological, and molecular quantities,…

Edge CMT: identifying genes that shape complex multigenic traits within and between yeast species - most phenotypic traits, including nearly all morphological, physiological, and molecular quantities, vary continuously among individuals in a population. These traits are shaped by DNA variation at dozens to thousands of genes, giving them a complex, multigenic basis. Over the past 20 years, there has been remarkable progress in identifying genomic regions that are associated with complex traits. However, few of the causal genes that shape complex traits have been identified. This proposal addresses this key problem by introducing a new method for genetic mapping called CRI-SPA-map. Our objectives are to apply CRI-SPA-map in three distinct, complementary contexts in the yeast saccharomyces cerevisiae: a pair of closely related strains, a pair of more distantly related strains, and between s. Cerevisiae and its reproductively isolated sister species s. Paradoxus. In each of these contexts, we will identify and analyze causal genes that shape the ability of yeast strains to grow in a set of diverse environmental conditions. CRI-SPA-map makes IT possible to transfer small tracts of DNA from one yeast strain to a genetically different strain efficiently, in high throughput, and with minimal cost. Combined with high-throughput phenotyping, CRI-SPA-map enables systematic discovery of causal genes that shape complex traits. We anticipate that our proposed activities will result in discovery of dozens to hundreds of causal genes. Systematic analyses of these genes will provide new insights into the genetic architecture of complex multigenic traits, such as the precise number and effects of causal genes, how their functional roles relate to the given trait, and how their effects vary across conditions. This proposal will also generate a community resource of libraries of allele-engineered and whole-genome sequenced yeast strains, allowing mapping of any trait of interest to gene-level resolution. We will pursue two specific activities in support of the broader impacts of this proposal. In support of improved stem education, this grant will support a teaching experiment to test if the order in which genetic concepts are taught can improve student understanding of multigenic traits. In support of the development of a competitive stem workforce, this proposal will establish a new pathway for undergraduate research experiences in complex trait genetics. Relevance (see instructions): most phenotypic traits are shaped by DNA variation at dozens to thousands of genes, but few of the causal genes have been identified. This proposal addresses this key problem by introducing a new method for genetic mapping, which we will apply to reveal causal genes in three contexts in the yeast saccharomyces cerevisiae. Systematic analyses of these genes will provide new insights into the genetic architecture of complex multigenic traits.