Fig. 3

Mutations in GDH1 played a critical role in the evolution of SSL tolerance. a Seven independent mutations result in amino acid substitutions in the Gdh1 protein. Their evolutionary trajectories cluster into a high (blue) and low (red) frequency group. b The high-frequency group maps at the N-terminus of Gdh1p, while the low frequency cohort affects residues clustered at the C-terminus. c Mapping of the seven substitutions onto a homology model of Gdh1p reveals that they all cluster in or near the hinge connecting the two structural domains of the protein, an area rich with known ubiquitination sites (displayed in orange). d Introduction of the gdh1 mutations into haploid and diploid wild-type backgrounds leads to a loss of fitness. Removal of mutant gdh1 alleles from the SSL-tolerant R57 background is also associated with a loss of tolerance. Error bars represent ± 1 standard deviation