Protein Homeostasis and the Phenotypic Manifestation of Genetic Diversity: Principles and Mechanisms
Abstract
Changing a single nucleotide in a genome can have profound consequences under some conditions, but the same change can have no consequences under others. Indeed, organisms can be surprisingly robust to environmental and genetic perturbations. Yet, the mechanisms underlying such robustness are controversial. Moreover, how they might affect evolutionary change remains enigmatic. Here, we review the recently appreciated central role of protein homeostasis in buffering and potentiating genetic variation and discuss how these processes mediate the critical influence of the environment on the relationship between genotype and phenotype. Deciphering how robustness emerges from biological organization and the mechanisms by which it is overcome in changing environments will lead to a more complete understanding of both fundamental evolutionary processes and diverse human diseases.
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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 [129]
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 [129]
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From the genetic architecture to synaptic plasticity in autism spectrum disorder
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Antifungal Drug Resistance: Molecular Mechanisms in <i>Candida albicans</i> and Beyond
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Lysine Deacetylases Hda1 and Rpd3 Regulate Hsp90 Function thereby Governing Fungal Drug Resistance
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Single-cell transcriptogenomics reveals transcriptional exclusion of ENU-mutated alleles
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- Authors
- Jarosz, D. F., Taipale, M., & Lindquist, S.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Jarosz, Daniel F.
- Taipale, Mikko
- Venue
- Annual Review of Genetics
- Publisher
- Annual Reviews
- Published
- 2010-12-01
- Volume
- 44
- Issue
- 1
- Pages
- 189-216
- ISSN
- 0066-4197 (ISSN-L)
- 1545-2948
- OpenAlex
- W2147984622
- Cited by
- 179
- References
- 200
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 10 · 2023: 6 · 2022: 8 · 2021: 10 · 2020: 11 · 2019: 9 · 2018: 14 · 2017: 11 · 2016: 11 · 2015: 17 · 2014: 23 · 2013: 10 · 2012: 16
- FWCI
- 1.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Genetics (publishedVersion)
- PubMed (publishedVersion)
- 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 › RNA and protein synthesis mechanisms
- Keywords
- proteostasis, genetic robustness, genotype-phenotype correlation, environmental disturbance, evolutionary change, phenotypic plasticity, genetic diversity, human disease
- MeSH terms
- Animals, Biological Evolution, Homeostasis, Humans, Mutation, Phenotype, Proteins, Genetic Variation
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