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

Enhanced phenotypic diversity increases the likelihood of a population surviving catastrophic conditions. It has been suggested that Hsp90, an essential molecular chaperone in eukaryotes, can suppress (i.e., buffer) or enhance (i.e., potentiate) the effects of genetic variation, enabling organisms to adjust their levels of phenotypic diversity in response to environmental cues. Many Hsp90-interacting proteins are involved in signaling transduction pathways and transcriptional regulation. However, it remains unclear if Hsp90-dependent differential gene expression is common in natural populations. By examining the gene expression profiles of five diverse yeast strains, we identified many genes exhibiting Hsp90-dependent strain-specific differential expression. We employed an analysis pipeline to identify transcription factors (TFs) potentially contributing to variable expression. We found that upon Hsp90 inhibition or heat 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 populations can readily display specific Hsp90-dependent gene expression, suggesting that the evolutionary impacts of Hsp90 are widespread in nature. Highlights 1. Hsp90-dependent gene expression varies among different yeast strains. 2. Hsp90 differentially influences transcriptional activity or protein abundances of transcription factors among yeast strains. 3. Differential strain-specific gene expression is correlated with phenotypic variations upon Hsp90 inhibition. 4. Hsp90-mediated strain-specific regulation manifests under environmental stress. ### Competing Interest Statement The authors have declared no competing interest.