Ethanol Drives Evolution of Hsp90-Dependent Robustness by Redundancy in Yeast Domestication

Protein folding promotes and constrains adaptive evolution. We uncover this surprising duality in the role the protein-folding chaperone Hsp90 plays in mediating the interplay between proteome and the genome which acts to maintain the integrity of yeast metabolism in the face of proteotoxic stressors in anthropic niches. Of great industrial relevance, ethanol concentrations generated by fermentation in the making of beer and bread disrupt critical Hsp90-dependent nodes of metabolism and exert strong selective pressure for increased copy number of key genes encoding components of these nodes, yielding the classical genetic signatures of beer and bread domestication. This work establishes a mechanism of adaptive canalization in an ecology of major economic significance and highlights Hsp90-contingent variation as an important source of phantom heritability in complex traits.