ArticlePLoS biology2016
Selection Transforms the Landscape of Genetic Variation Interacting with Hsp90.
Article in PLoS biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 106 citations in OpenAlex.
- Consistent and idiosyncratic pleiotropy in shaping genetic correlations.Molecular biology and evolution · 2026Article
- Function-specific epistasis shapes evolutionary trajectories towards antibiotic resistance.Nature communications · 2026Article
- Gim3 buffers and potentiates de novo mutations that affect fluconazole susceptibility in yeast.EMBO reports · 2026Article
- Environment-by-Environment Interactions Differ Across Genetic Backgrounds.Molecular biology and evolution · 2025Article
- HSP90 as an evolutionary capacitor drives adaptive eye size reduction via atonal.Nature communications · 2025Article
- The Hsp90 Molecular Chaperone as a Global Modifier of the Genotype-Phenotype-Fitness Map: An Evolutionary Perspective.Journal of molecular biology · 2024Review
- Distinguishing mutants that resist drugs via different mechanisms by examining fitness tradeoffs.eLife · 2024Article
- Spontaneous single-nucleotide substitutions and microsatellite mutations have distinct distributions of fitness effects.PLoS biology · 2024Article
- Distinguishing mutants that resist drugs via different mechanisms by examining fitness tradeoffs.bioRxiv : the preprint server for biology · 2024Article
- Mutational robustness and the role of buffer genes in evolvability.The EMBO journal · 2024Review
- Detecting natural selection in trait-trait coevolution.BMC ecology and evolution · 2023Article
- The effect of mutational robustness on the evolvability of multicellular organisms and eukaryotic cells.Journal of evolutionary biology · 2023Article
- Differential Hsp90-dependent gene expression is strain-specific and common among yeast strains.iScience · 2023Article
- Article
- GroEL/S Overexpression Helps to Purge Deleterious Mutations and Reduce Genetic Diversity during Adaptive Protein Evolution.Molecular biology and evolution · 2022Article
- Genetic basis of a spontaneous mutation's expressivity.Genetics · 2022Article
- High-throughput platform for yeast morphological profiling predicts the targets of bioactive compounds.NPJ systems biology and applications · 2022Article
- Universal Constraints on Protein Evolution in the Long-Term Evolution Experiment with Escherichia coli.Genome biology and evolution · 2021Article
- Cryptic genetic variation in a heat shock protein modifies the outcome of a mutation affecting epidermal stem cell development in C. elegans.Nature communications · 2021Article
- Constructive Neutral Evolution 20 Years Later.Journal of molecular evolution · 2021Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The protein-folding chaperone Hsp90 has been proposed to buffer the phenotypic effects of mutations. The potential for Hsp90 and other putative buffers to increase robustness to mutation has had major impact on disease models, quantitative genetics, and evolutionary theory. But Hsp90 sometimes contradicts expectations for a buffer by potentiating rapid phenotypic changes that would otherwise not occur. Here, we quantify Hsp90's ability to buffer or potentiate (i.e., diminish or enhance) the effects of genetic variation on single-cell morphological features in budding yeast. We corroborate reports that Hsp90 tends to buffer the effects of standing genetic variation in natural populations. However, we demonstrate that Hsp90 tends to have the opposite effect on genetic variation that has experienced reduced selection pressure. Specifically, Hsp90 tends to enhance, rather than diminish, the effects of spontaneous mutations and recombinations. This result implies that Hsp90 does not make phenotypes more robust to the effects of genetic perturbation. Instead, natural selection preferentially allows buffered alleles to persist and thereby creates the false impression that Hsp90 confers greater robustness.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.