The distribution of beneficial mutational effects between two sister yeast species poorly explains natural outcomes of vineyard adaptation.

Domesticated strains of have adapted to resist copper and sulfite, two chemical stressors commonly used in winemaking. , has not adapted to these chemicals despite being consistently present in sympatry with in vineyards. This contrast represents a case of apparent evolutionary constraints favoring greater adaptive capacity in . In this study, we used a comparative mutagenesis approach to test whether is mutationally constrained with respect to acquiring greater copper and sulfite resistance. For both species, we assayed the rate, effect size, and pleiotropic costs of resistance mutations and sequenced a subset of 150 mutants isolated from our screen. We found that the distributions of mutational effects displayed by the two species were very similar and poorly explained the natural pattern. We also found that chromosome VIII aneuploidy and loss of function mutations in confer copper resistance in both species, whereas loss of function mutations in were only a viable route to copper resistance in . We also observed a single duplication of the gene in but none in . For sulfite, loss of function mutations in and confer resistance in both species, but mutations in have larger average effects in . Our results show that even when the distributions of mutational effects are largely similar, species can differ in the adaptive paths available to them. They also demonstrate that assays of the distribution of mutational effects may lack predictive insight concerning adaptive outcomes.