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      Mutational robustness and the role of buffer genes in evolvability

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          Abstract

          Organisms rely on mutations to fuel adaptive evolution. However, many mutations impose a negative effect on fitness. Cells may have therefore evolved mechanisms that affect the phenotypic effects of mutations, thus conferring mutational robustness. Specifically, so-called buffer genes are hypothesized to interact directly or indirectly with genetic variation and reduce its effect on fitness. Environmental or genetic perturbations can change the interaction between buffer genes and genetic variation, thereby unmasking the genetic variation’s phenotypic effects and thus providing a source of variation for natural selection to act on. This review provides an overview of our understanding of mutational robustness and buffer genes, with the chaperone gene HSP90 as a key example. It discusses whether buffer genes merely affect standing variation or also interact with de novo mutations, how mutational robustness could influence evolution, and whether mutational robustness might be an evolved trait or rather a mere side-effect of complex genetic interactions.

          Abstract

          This review uses the example of the chaperone gene HSP90 to outline our current understanding of mutational robustness and the role of buffer genes in evolution.

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          Instability and decay of the primary structure of DNA.

          T Lindahl (1993)
          Although DNA is the carrier of genetic information, it has limited chemical stability. Hydrolysis, oxidation and nonenzymatic methylation of DNA occur at significant rates in vivo, and are counteracted by specific DNA repair processes. The spontaneous decay of DNA is likely to be a major factor in mutagenesis, carcinogenesis and ageing, and also sets limits for the recovery of DNA fragments from fossils.
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            Hsp90 as a capacitor of phenotypic variation.

            Heat-shock protein 90 (Hsp90) chaperones the maturation of many regulatory proteins and, in the fruitfly Drosophila melanogaster, buffers genetic variation in morphogenetic pathways. Levels and patterns of genetic variation differ greatly between obligatorily outbreeding species such as fruitflies and self-fertilizing species such as the plant Arabidopsis thaliana. Also, plant development is more plastic, being coupled to environmental cues. Here we report that, in Arabidopsis accessions and recombinant inbred lines, reducing Hsp90 function produces an array of morphological phenotypes, which are dependent on underlying genetic variation. The strength and breadth of Hsp90's effects on the buffering and release of genetic variation suggests it may have an impact on evolutionary processes. We also show that Hsp90 influences morphogenetic responses to environmental cues and buffers normal development from destabilizing effects of stochastic processes. Manipulating Hsp90's buffering capacity offers a tool for harnessing cryptic genetic variation and for elucidating the interplay between genotypes, environments and stochastic events in the determination of phenotype.
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              Canalization of Development and the Inheritance of Acquired Characters

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                Author and article information

                Contributors
                Kevin.Verstrepen@kuleuven.be
                Journal
                EMBO J
                EMBO J
                The EMBO Journal
                Nature Publishing Group UK (London )
                0261-4189
                1460-2075
                8 May 2024
                8 May 2024
                June 2024
                : 43
                : 12
                : 2294-2307
                Affiliations
                [1 ]VIB-KU Leuven Center for Microbiology, ( https://ror.org/02bpp8r91) Leuven, Belgium
                [2 ]Department of Microbial and Molecular Systems, KU Leuven, ( https://ror.org/05f950310) Leuven, Belgium
                [3 ]Department of Biology, KU Leuven, ( https://ror.org/05f950310) Leuven, Belgium
                Author information
                http://orcid.org/0000-0001-9504-5284
                http://orcid.org/0000-0001-6397-840X
                http://orcid.org/0000-0001-7886-9345
                http://orcid.org/0000-0002-3077-6219
                Article
                109
                10.1038/s44318-024-00109-1
                11183146
                38719995
                53eca3b6-7b7a-4630-894d-86502807a77d
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Creative Commons Public Domain Dedication waiver http://creativecommons.org/publicdomain/zero/1.0/ applies to the data associated with this article, unless otherwise stated in a credit line to the data, but does not extend to the graphical or creative elements of illustrations, charts, or figures. This waiver removes legal barriers to the re-use and mining of research data. According to standard scholarly practice, it is recommended to provide appropriate citation and attribution whenever technically possible.

                History
                : 8 November 2023
                : 19 March 2024
                : 17 April 2024
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100003130, Fonds Wetenschappelijk Onderzoek (FWO);
                Award ID: (Grant No. 11H1823N)
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100004040, KU Leuven (Katholieke Universiteit Leuven);
                Award ID: C1 grant (C16/23/007)
                Award ID: C1 grant (C16/23/007)
                Award ID: C1 grant (C16/23/007)
                Award ID: C1 grant (C16/23/007)
                Award Recipient :
                Categories
                Review Article
                Custom metadata
                © European Molecular Biology Organization 2024

                Molecular biology
                cryptic genetic variation,evolvability,genetic buffering,hsp90,mutational robustness,evolution & ecology

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