Dissecting the Pleiotropic Consequences of a Quantitative Trait Nucleotide

The downstream consequences of a single quantitative trait polymorphism can provide important insight into the molecular basis of a trait. However, the molecular consequences of a polymorphism may be complex and only a subset of these may influence the trait of interest. In natural isolates of Saccharomyces cerevisiae, a nonsynonymous polymorphism in cystathione beta-synthase (CYS4) causes a deficiency in both cysteine and glutathione that results in rust-colored colonies and drug-dependent growth defects. Using a single-nucleotide allele replacement, we characterized the effects of this polymorphism on gene expression levels across the genome. To determine whether any of the differentially expressed genes are necessary for the production of rust-colored colonies, we screened the yeast deletion collection for genes that enhance or suppress rust coloration. We found that genes in the sulfur assimilation pathway are required for the production of rust color but not the drug-sensitivity phenotype. Our results show that a single quantitative trait polymorphism can generate a complex set of downstream changes, providing a molecular basis for pleiotropy.