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. 2010 Dec 24;330(6012):1820-4.
doi: 10.1126/science.1195487.

Hsp90 and environmental stress transform the adaptive value of natural genetic variation

Daniel F Jarosz  1 , Susan Lindquist
Affiliations

Hsp90 and environmental stress transform the adaptive value of natural genetic variation

Daniel F Jarosz et al. Science. .

Abstract

How can species remain unaltered for long periods yet also undergo rapid diversification? By linking genetic variation to phenotypic variation via environmental stress, the Hsp90 protein-folding reservoir might promote both stasis and change. However, the nature and adaptive value of Hsp90-contingent traits remain uncertain. In ecologically and genetically diverse yeasts, we find such traits to be both common and frequently adaptive. Most are based on preexisting variation, with causative polymorphisms occurring in coding and regulatory sequences alike. A common temperature stress alters phenotypes similarly. Both selective inhibition of Hsp90 and temperature stress increase correlations between genotype and phenotype. This system broadly determines the adaptive value of standing genetic variation and, in so doing, has influenced the evolution of current genomes.

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Figures

Fig. 1
Fig. 1
Reducing the Hsp90 reservoir creates diverse phenotypes. Representative growth changes elicited by Hsp90 inhibition. The scale bar indicates log2 of the ratio of growth in each condition with and without 5 mM Rad for (A) wild strains and (B) BY × RM progeny. (C to F) Examples of rank-ordered growth distributions after 64 hours of growth of BY × RM progeny with (orange bars) and without (gray bars) 5 mM Rad.
Fig. 2
Fig. 2
Genetic dissection of Hsp90-contingent alleles. The growth of allele-replacement strains with (solid bars) and without (open bars) 5 mM Rad is normalized to that of the BY allele–replacement strain in each condition without Rad. (A) QTLs conferring Hsp90-buffered rapamycin resistance, due to the RM NFS1 allele (44 hours). (B) QTLs conferring Hsp90-potentiated DOC resistance, due to the RM PDR8 allele. (C). QTLs conferring Hsp90-buffered HU resistance, due to the BY MEC1 allele (25 hours). Hsp90-potentiated resistance to UV-irradiation was due to the same allele (20 J/m2; 25 hours after irradiation). (D) QTLs conferring CDNB resistance, due to polymorphisms in the 3′-untranslated region (UTR) of RM NDI1 (44 hours). Overexpression of BY NDI1 rescues CDNB toxicity. Error bars in the entire figure represent the standard deviation of three biological replicates.
Fig. 3
Fig. 3
Environmental stress recapitulates phenotypic effects of Hsp90 inhibition. Calculations and symbols are as in Fig. 2. Growth of allele-replacement strains at 23°C, 39°C, or after a deletion of one of the Hsp90 genes, Hsp82, at 23°C, is shown. (A) NFS1 (0.5 μM rapamycin; 44 hours). (B) PDR8 (1 mM DOC; 80 hours). (C) MEC1 (25 mM HU; 25 hours) (D) RM intergenic region between NDI1 and GTR1 (5 mM CDNB; 44 hours). Because the HSP82 deletion reduces Hsp90 function more than does 5 μM Rad, it often creates stronger phenotypes.
Fig. 4
Fig. 4
Hsp90 inhibition and environmental stress improve the corrrelations between genotype and phenotype. Phylogenetic clustering is derived from (27) and (25). Phenotypic clustering is described in the SOM.
See this image and copyright information in PMC

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