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Nonlinear Fitness Consequences of Variation in Expression Level of a Eukaryotic Gene

Levels of gene expression show considerable variation in eukaryotes, but no fine-scale maps have been made of the fitness consequences of such variation in controlled genetic backgrounds and environments. To address this, we assayed fitness at many levels of up- and down-regulated expression of a si...

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Autores principales: Rest, Joshua S., Morales, Christopher M., Waldron, John B., Opulente, Dana A., Fisher, Julius, Moon, Seungjae, Bullaughey, Kevin, Carey, Lucas B., Dedousis, Demitri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548308/
https://www.ncbi.nlm.nih.gov/pubmed/23104081
http://dx.doi.org/10.1093/molbev/mss248
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author Rest, Joshua S.
Morales, Christopher M.
Waldron, John B.
Opulente, Dana A.
Fisher, Julius
Moon, Seungjae
Bullaughey, Kevin
Carey, Lucas B.
Dedousis, Demitri
author_facet Rest, Joshua S.
Morales, Christopher M.
Waldron, John B.
Opulente, Dana A.
Fisher, Julius
Moon, Seungjae
Bullaughey, Kevin
Carey, Lucas B.
Dedousis, Demitri
author_sort Rest, Joshua S.
collection PubMed
description Levels of gene expression show considerable variation in eukaryotes, but no fine-scale maps have been made of the fitness consequences of such variation in controlled genetic backgrounds and environments. To address this, we assayed fitness at many levels of up- and down-regulated expression of a single essential gene, LCB2, involved in sphingolipid synthesis in budding yeast Saccharomyces cerevisiae. Reduced LCB2 expression rapidly decreases cellular fitness, yet increased expression has little effect. The wild-type expression level is therefore perched on the edge of a nonlinear fitness cliff. LCB2 is upregulated when cells are exposed to osmotic stress; consistent with this, the entire fitness curve is shifted upward to higher expression under osmotic stress, illustrating the selective force behind gene regulation. Expression levels of LCB2 are lower in wild yeast strains than in the experimental lab strain, suggesting that higher levels in the lab strain may be idiosyncratic. Reports indicate that the effect sizes of alleles contributing to variation in complex phenotypes differ among environments and genetic backgrounds; our results suggest that such differences may be explained as simple shifts in the position of nonlinear fitness curves.
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spelling pubmed-35483082013-01-18 Nonlinear Fitness Consequences of Variation in Expression Level of a Eukaryotic Gene Rest, Joshua S. Morales, Christopher M. Waldron, John B. Opulente, Dana A. Fisher, Julius Moon, Seungjae Bullaughey, Kevin Carey, Lucas B. Dedousis, Demitri Mol Biol Evol Discoveries Levels of gene expression show considerable variation in eukaryotes, but no fine-scale maps have been made of the fitness consequences of such variation in controlled genetic backgrounds and environments. To address this, we assayed fitness at many levels of up- and down-regulated expression of a single essential gene, LCB2, involved in sphingolipid synthesis in budding yeast Saccharomyces cerevisiae. Reduced LCB2 expression rapidly decreases cellular fitness, yet increased expression has little effect. The wild-type expression level is therefore perched on the edge of a nonlinear fitness cliff. LCB2 is upregulated when cells are exposed to osmotic stress; consistent with this, the entire fitness curve is shifted upward to higher expression under osmotic stress, illustrating the selective force behind gene regulation. Expression levels of LCB2 are lower in wild yeast strains than in the experimental lab strain, suggesting that higher levels in the lab strain may be idiosyncratic. Reports indicate that the effect sizes of alleles contributing to variation in complex phenotypes differ among environments and genetic backgrounds; our results suggest that such differences may be explained as simple shifts in the position of nonlinear fitness curves. Oxford University Press 2013-02 2012-10-27 /pmc/articles/PMC3548308/ /pubmed/23104081 http://dx.doi.org/10.1093/molbev/mss248 Text en © The Author(s) 2012. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Discoveries
Rest, Joshua S.
Morales, Christopher M.
Waldron, John B.
Opulente, Dana A.
Fisher, Julius
Moon, Seungjae
Bullaughey, Kevin
Carey, Lucas B.
Dedousis, Demitri
Nonlinear Fitness Consequences of Variation in Expression Level of a Eukaryotic Gene
title Nonlinear Fitness Consequences of Variation in Expression Level of a Eukaryotic Gene
title_full Nonlinear Fitness Consequences of Variation in Expression Level of a Eukaryotic Gene
title_fullStr Nonlinear Fitness Consequences of Variation in Expression Level of a Eukaryotic Gene
title_full_unstemmed Nonlinear Fitness Consequences of Variation in Expression Level of a Eukaryotic Gene
title_short Nonlinear Fitness Consequences of Variation in Expression Level of a Eukaryotic Gene
title_sort nonlinear fitness consequences of variation in expression level of a eukaryotic gene
topic Discoveries
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548308/
https://www.ncbi.nlm.nih.gov/pubmed/23104081
http://dx.doi.org/10.1093/molbev/mss248
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