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Selection Transforms the Landscape of Genetic Variation Interacting with Hsp90

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 contr...

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Autores principales: Geiler-Samerotte, Kerry A., Zhu, Yuan O., Goulet, Benjamin E., Hall, David W., Siegal, Mark L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5074785/
https://www.ncbi.nlm.nih.gov/pubmed/27768682
http://dx.doi.org/10.1371/journal.pbio.2000465
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author Geiler-Samerotte, Kerry A.
Zhu, Yuan O.
Goulet, Benjamin E.
Hall, David W.
Siegal, Mark L.
author_facet Geiler-Samerotte, Kerry A.
Zhu, Yuan O.
Goulet, Benjamin E.
Hall, David W.
Siegal, Mark L.
author_sort Geiler-Samerotte, Kerry A.
collection PubMed
description 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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spelling pubmed-50747852016-11-04 Selection Transforms the Landscape of Genetic Variation Interacting with Hsp90 Geiler-Samerotte, Kerry A. Zhu, Yuan O. Goulet, Benjamin E. Hall, David W. Siegal, Mark L. PLoS Biol Research Article 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. Public Library of Science 2016-10-21 /pmc/articles/PMC5074785/ /pubmed/27768682 http://dx.doi.org/10.1371/journal.pbio.2000465 Text en © 2016 Geiler-Samerotte et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Geiler-Samerotte, Kerry A.
Zhu, Yuan O.
Goulet, Benjamin E.
Hall, David W.
Siegal, Mark L.
Selection Transforms the Landscape of Genetic Variation Interacting with Hsp90
title Selection Transforms the Landscape of Genetic Variation Interacting with Hsp90
title_full Selection Transforms the Landscape of Genetic Variation Interacting with Hsp90
title_fullStr Selection Transforms the Landscape of Genetic Variation Interacting with Hsp90
title_full_unstemmed Selection Transforms the Landscape of Genetic Variation Interacting with Hsp90
title_short Selection Transforms the Landscape of Genetic Variation Interacting with Hsp90
title_sort selection transforms the landscape of genetic variation interacting with hsp90
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5074785/
https://www.ncbi.nlm.nih.gov/pubmed/27768682
http://dx.doi.org/10.1371/journal.pbio.2000465
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