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Expression attenuation as a mechanism of robustness against gene duplication

Gene duplication is ubiquitous and a major driver of phenotypic diversity across the tree of life, but its immediate consequences are not fully understood. Deleterious effects would decrease the probability of retention of duplicates and prevent their contribution to long-term evolution. One possibl...

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Autores principales: Ascencio, Diana, Diss, Guillaume, Gagnon-Arsenault, Isabelle, Dubé, Alexandre K., DeLuna, Alexander, Landry, Christian R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970654/
https://www.ncbi.nlm.nih.gov/pubmed/33526669
http://dx.doi.org/10.1073/pnas.2014345118
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author Ascencio, Diana
Diss, Guillaume
Gagnon-Arsenault, Isabelle
Dubé, Alexandre K.
DeLuna, Alexander
Landry, Christian R.
author_facet Ascencio, Diana
Diss, Guillaume
Gagnon-Arsenault, Isabelle
Dubé, Alexandre K.
DeLuna, Alexander
Landry, Christian R.
author_sort Ascencio, Diana
collection PubMed
description Gene duplication is ubiquitous and a major driver of phenotypic diversity across the tree of life, but its immediate consequences are not fully understood. Deleterious effects would decrease the probability of retention of duplicates and prevent their contribution to long-term evolution. One possible detrimental effect of duplication is the perturbation of the stoichiometry of protein complexes. Here, we measured the fitness effects of the duplication of 899 essential genes in the budding yeast using high-resolution competition assays. At least 10% of genes caused a fitness disadvantage when duplicated. Intriguingly, the duplication of most protein complex subunits had small to nondetectable effects on fitness, with few exceptions. We selected four complexes with subunits that had an impact on fitness when duplicated and measured the impact of individual gene duplications on their protein–protein interactions. We found that very few duplications affect both fitness and interactions. Furthermore, large complexes such as the 26S proteasome are protected from gene duplication by attenuation of protein abundance. Regulatory mechanisms that maintain the stoichiometric balance of protein complexes may protect from the immediate effects of gene duplication. Our results show that a better understanding of protein regulation and assembly in complexes is required for the refinement of current models of gene duplication.
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spelling pubmed-79706542021-03-25 Expression attenuation as a mechanism of robustness against gene duplication Ascencio, Diana Diss, Guillaume Gagnon-Arsenault, Isabelle Dubé, Alexandre K. DeLuna, Alexander Landry, Christian R. Proc Natl Acad Sci U S A Biological Sciences Gene duplication is ubiquitous and a major driver of phenotypic diversity across the tree of life, but its immediate consequences are not fully understood. Deleterious effects would decrease the probability of retention of duplicates and prevent their contribution to long-term evolution. One possible detrimental effect of duplication is the perturbation of the stoichiometry of protein complexes. Here, we measured the fitness effects of the duplication of 899 essential genes in the budding yeast using high-resolution competition assays. At least 10% of genes caused a fitness disadvantage when duplicated. Intriguingly, the duplication of most protein complex subunits had small to nondetectable effects on fitness, with few exceptions. We selected four complexes with subunits that had an impact on fitness when duplicated and measured the impact of individual gene duplications on their protein–protein interactions. We found that very few duplications affect both fitness and interactions. Furthermore, large complexes such as the 26S proteasome are protected from gene duplication by attenuation of protein abundance. Regulatory mechanisms that maintain the stoichiometric balance of protein complexes may protect from the immediate effects of gene duplication. Our results show that a better understanding of protein regulation and assembly in complexes is required for the refinement of current models of gene duplication. National Academy of Sciences 2021-02-09 2021-02-01 /pmc/articles/PMC7970654/ /pubmed/33526669 http://dx.doi.org/10.1073/pnas.2014345118 Text en Copyright © 2021 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Ascencio, Diana
Diss, Guillaume
Gagnon-Arsenault, Isabelle
Dubé, Alexandre K.
DeLuna, Alexander
Landry, Christian R.
Expression attenuation as a mechanism of robustness against gene duplication
title Expression attenuation as a mechanism of robustness against gene duplication
title_full Expression attenuation as a mechanism of robustness against gene duplication
title_fullStr Expression attenuation as a mechanism of robustness against gene duplication
title_full_unstemmed Expression attenuation as a mechanism of robustness against gene duplication
title_short Expression attenuation as a mechanism of robustness against gene duplication
title_sort expression attenuation as a mechanism of robustness against gene duplication
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970654/
https://www.ncbi.nlm.nih.gov/pubmed/33526669
http://dx.doi.org/10.1073/pnas.2014345118
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