Hsp90 and Environmental Stress Transform the Adaptive Value of Natural Genetic Variation

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.

Sequence-based association and selection scans identify drug resistance loci in the Plasmodium falciparum malaria parasite

“…Field-based evidence has demonstrated a reduced fitness for drug-resistant parasites in the absence of drug pressure, and laboratory-based work has demonstrated the relative fitness of different mutational changes in target enzymes. Our findings point to potential compensatory mutations in a pathway related to protein stability and turnover, and it is tempting to speculate that such adaptations enable the "expression" of a resistant phenotype, such as has been observed in yeast (35). Although molecular approaches are required to validate the role of this pathway in modulating drug response, these results demonstrate the potential for sequence-based GWAS approaches to identify pathways, in addition to individual genes, that may be responsible for the phenotype of interest.…”

Effects of larval crowding on quantitative variation for development time and viability in Drosophila melanogaster

“…A potential explanation lies in the highly polygenic nature of life‐history traits; it creates the opportunity for ample amount of nonadditive genetic variation—dominance, epistatic, and genotype‐by‐environment interactions (GEIs)—to exist. Recently, there have been studies quantifying dominance effects and epistasis (Armbruster, Bradshaw, & Holzapfel, 1997; Huang et al., 2012; Monnahan & Kelly, 2015), as well as the role of GEI in adaptation (e.g., Gutteling, Riksen, Bakker, & Kammenga, 2007; Jarosz & Lindquist, 2010; Rohner et al., 2013; for a review see Schlichting, 2008). Despite that, the pervasiveness of additive‐ and nonadditive variation—particularly for competitive traits—is still not yet well understood, especially in the context of environmental changes.…”

The Protein Chaperone HSP90 Can Facilitate the Divergence of Gene Duplicates

“…This trend was not detected when yeast clients and nonclients were compared without considering paralog status. Our data provide evidence that HSP90 influences selection on genes encoding its clients and facilitates divergence between gene duplicates.T HE phenotypic capacitor heat-shock protein 90 (HSP90) is thought to influence evolutionary processes through its ability to both conceal and release genetic variation (Rutherford and Lindquist 1998;Queitsch et al 2002;Yeyati et al 2007;Jarosz and Lindquist 2010). Perturbation of this conserved and essential chaperone reveals cryptic genetic and epigenetic variation in flies, plants, fish, and yeast (Rutherford and Lindquist 1998;Queitsch et al 2002;Sollars et al 2003;Yeyati et al 2007;Jarosz and Lindquist 2010).…”