Gene-level Dissection of a Complex Trait

Abstract

Complex traits are ubiquitous in nature; however basic questions about their heritability and evolution remain unanswered. Here we develop a reciprocal hemizygosity assay to dissect quantitative trait loci (QTL) that contribute to tunicamycin resistance in the budding yeast Saccharomyces cerevisiae. Gene-level molecular dissection of two QTL identified five neighboring genes and a sixth unlinked gene with allele-specific growth effects in tunicamycin stress conditions in a cross between the lab strain BY4742 and the wine strain RM11_1a. Furthermore, four alleles showed evidence of fitness tradeoffs between growth in rich medium and growth in stress conditions. Together, our findings suggest the importance of genome architecture and evolutionary history in the inheritance of complex traits in yeast and higher organisms.