Differential Hsp90-dependent gene expression is strain-specific and common among yeast strains.

Enhanced phenotypic diversity increases a population's likelihood of surviving catastrophic conditions. Hsp90, an essential molecular chaperone and a central network hub in eukaryotes, has been observed to suppress or enhance the effects of genetic variation on phenotypic diversity in response to environmental cues. Because many Hsp90-interacting genes are involved in signaling transduction pathways and transcriptional regulation, we tested how common Hsp90-dependent differential gene expression is in natural populations. Many genes exhibited Hsp90-dependent strain-specific differential expression in five diverse yeast strains. We further identified transcription factors (TFs) potentially contributing to variable expression. We found that on Hsp90 inhibition or environmental stress, activities or abundances of Hsp90-dependent TFs varied among strains, resulting in differential strain-specific expression of their target genes, which consequently led to phenotypic diversity. We provide evidence that individual strains can readily display specific Hsp90-dependent gene expression, suggesting that the evolutionary impacts of Hsp90 are widespread in nature.