Hsp90 and Environmental Stress Transform the Adaptive Value of Natural Genetic Variation
Open accessAbstract
Exploiting Variation: Molecular chaperones help newly synthesized proteins fold, protecting the macromolecular machinery of the cell from various stresses; for example, the highly conserved heat shock proteins (hsp) protect against elevated temperature. Hsp90 has also been suggested both to buffer against and to potentiate existing genetic variation in a population. To investigate the generality of these claims, Jarosz and Lindquist (p. 1820 ) screened 96 Saccharomyces cerevisiae strains from various ecological niches—soil, fruit, sake, beer, and infected humans—as well as assessed their adaptive value under different growth conditions. Hsp90 determined the adaptive value of ∼20% of the genetic variation in baker's yeast, with half of the traits being buffered, and half potentiated by hsp90.
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Hsp90 is thought to generate "protein-folding reservoirs" that can buffer the phenotypic impact of mutations in client proteins, thereby facilitating evolutionary change.
“As a direct consequence of its role in maintaining the structural integrity of its client proteins, Hsp90 is thought to generate “protein-folding reservoirs” that can buffer the phenotypic impact of mutations in client proteins, thereby facilitating evolutionary change18.”
From Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal inputs (2012) · cites this paper as [18]
Hsp90 influences approximately 20% of natural genetic variation in S. cerevisiae, serving both to maintain phenotypic robustness and promote diversification.
“A recent study exploiting the genetic tractability of S. cerevisiae, revealed that Hsp90 influences approximately 20% of natural genetic variation serving both to maintain phenotypic robustness and promote diversification18.”
From Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal inputs (2012) · cites this paper as [18]
Hsp90 can buffer the effects of genetic or epigenetic variation, keeping it silent until released when the chaperone reservoir is compromised in response to stress.
“First, Hsp90 can buffer the effects of genetic or epigenetic variation, keeping it silent until released when the chaperone reservoir is compromised in response to stress.”
From Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal inputs (2012) · cites this paper as [18]
Hsp90's role as a capacitor for variation has been observed in diverse eukaryotes including flies, plants, and fungi.
“This role as a capacitor for variation has been observed in diverse eukaryotes including flies, plants, and fungi18,19,129-134.”
From Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal inputs (2012) · cites this paper as [18]
DNA replication itself is a process of high fidelity with a mutation rate of approximately 10^-10 per base pair per replication for microbial cells.
“Although DNA replication itself is a process of high fidelity with a mutation rate of approximately 10-10 per base pair per replication for microbial cells [127]”
From Adaptive laboratory evolution—Principles and applications for biotechnology (2013) · cites this paper as [127]
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- Authors
- Jarosz, D. F., & Lindquist, S.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Lindquist, Susan
- ORCID
- Jarosz, Daniel F.
- Venue
- Science
- Published
- 2010-12-24
- Volume
- 330
- Issue
- 6012
- Pages
- 1820-1824
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3260023
- OpenAlex
- W1550678611
- Cited by
- 346
- References
- 27
- Citations by year
- 2026: 10 · 2025: 14 · 2024: 23 · 2023: 16 · 2022: 13 · 2021: 12 · 2020: 12 · 2019: 24 · 2018: 31 · 2017: 19 · 2016: 21 · 2015: 29 · 2014: 32 · 2013: 35 · 2012: 34
- FWCI
- 16.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- PMC
- Funders
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- HSP90, environmental stress, natural genetic variation, adaptive significance, standing genetic variation, yeast, temperature stress, genotype-phenotype correlation, HSP90 inhibition, protein folding, regulatory polymorphisms
- MeSH terms
- Adaptation, Physiological, Crosses, Genetic, Deoxycholic Acid, Biological Evolution, Hydroxyurea, Microtubule-Associated Proteins, Polymorphism, Genetic, Saccharomyces cerevisiae, Stress, Physiological, Sulfurtransferases, Genetic Variation, Open Reading Frames, Protein Serine-Threonine Kinases, HSP90 Heat-Shock Proteins, Sirolimus, Mitochondrial Proteins, Drug Resistance, Fungal, Saccharomyces cerevisiae Proteins, Quantitative Trait Loci, Intracellular Signaling Peptides and Proteins
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