UCLA

Variation in nutrient availability between environments has led to the evolution of diverse metabolic pathways. These pathways differ across species, but are expected to be similar within a species. To identify large genetic differences in pathways within a single species, We performed a genome-wide scan for higher-order genetic interactions in segregants from 16 highly diverse S. cerevisiae crosses grown in 38 different conditions. We observed a large effect genetic interaction for growth in galactose among three loci in crosses involving the soil strain CBS2888. We used precisely engineered alleles to show that this genetic interac- tion arises from variation in the genes GAL2, GAL1/10/7, and PGM1 from the galactose metabolic pathway. The CBS2888 alleles of these galactose genes were highly diverged from the reference. We hereafter refer to the divergent galactose alleles found in CBS2888 as the alternative alleles, and the alleles found in other strains as the reference alleles. Strains with alternative alleles are found primarily in galactose-rich dairy environments, and they grow faster in galactose, but slower in glucose, revealing a tradeoff, on which population genetics analyses suggest that balancing selection could have acted on. Our results show that bal- ancing selection can preserve, functionally distinct states of a multi-locus genetic network, providing a general mechanism for maintenance of complex, interacting genetic variation at co-adapted alleles.