Metabolic pathways differ between species, but are expected to be similar within a species. We discovered two functional, incompatible versions of the galactose pathway in S. cerevisiae. We identified a 3-locus genetic interaction for growth in galactose, and used precisely engineered alleles to show that is arises from variation in the metabolic genes GAL2, GAL1/10/7, and PGM1, and that the reference allele of PGM1 is incompatible with the alternative alleles of the other genes. Multi-locus balancing selection has maintained the two incompatible versions of the pathway for millions of years. 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 balancing selection may have acted.

This dataset contains all the files necessary to recreate the figures in Boocock et al "Ancient balancing selection maintains incompatible versions of the galactose pathway in yeast".