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Characterizing selective pressures on the pathway for de novo biosynthesis of pyrimidines in yeast

BACKGROUND: Selection on proteins is typically measured with the assumption that each protein acts independently. However, selection more likely acts at higher levels of biological organization, requiring an integrative view of protein function. Here, we built a kinetic model for de novo pyrimidine...

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Autores principales: Hermansen, Russell A., Mannakee, Brian K., Knecht, Wolfgang, Liberles, David A., Gutenkunst, Ryan N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4625875/
https://www.ncbi.nlm.nih.gov/pubmed/26511837
http://dx.doi.org/10.1186/s12862-015-0515-x
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author Hermansen, Russell A.
Mannakee, Brian K.
Knecht, Wolfgang
Liberles, David A.
Gutenkunst, Ryan N.
author_facet Hermansen, Russell A.
Mannakee, Brian K.
Knecht, Wolfgang
Liberles, David A.
Gutenkunst, Ryan N.
author_sort Hermansen, Russell A.
collection PubMed
description BACKGROUND: Selection on proteins is typically measured with the assumption that each protein acts independently. However, selection more likely acts at higher levels of biological organization, requiring an integrative view of protein function. Here, we built a kinetic model for de novo pyrimidine biosynthesis in the yeast Saccharomyces cerevisiae to relate pathway function to selective pressures on individual protein-encoding genes. RESULTS: Gene families across yeast were constructed for each member of the pathway and the ratio of nonsynonymous to synonymous nucleotide substitution rates (dN/dS) was estimated for each enzyme from S. cerevisiae and closely related species. We found a positive relationship between the influence that each enzyme has on pathway function and its selective constraint. CONCLUSIONS: We expect this trend to be locally present for enzymes that have pathway control, but over longer evolutionary timescales we expect that mutation-selection balance may change the enzymes that have pathway control. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12862-015-0515-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-46258752015-10-30 Characterizing selective pressures on the pathway for de novo biosynthesis of pyrimidines in yeast Hermansen, Russell A. Mannakee, Brian K. Knecht, Wolfgang Liberles, David A. Gutenkunst, Ryan N. BMC Evol Biol Research Article BACKGROUND: Selection on proteins is typically measured with the assumption that each protein acts independently. However, selection more likely acts at higher levels of biological organization, requiring an integrative view of protein function. Here, we built a kinetic model for de novo pyrimidine biosynthesis in the yeast Saccharomyces cerevisiae to relate pathway function to selective pressures on individual protein-encoding genes. RESULTS: Gene families across yeast were constructed for each member of the pathway and the ratio of nonsynonymous to synonymous nucleotide substitution rates (dN/dS) was estimated for each enzyme from S. cerevisiae and closely related species. We found a positive relationship between the influence that each enzyme has on pathway function and its selective constraint. CONCLUSIONS: We expect this trend to be locally present for enzymes that have pathway control, but over longer evolutionary timescales we expect that mutation-selection balance may change the enzymes that have pathway control. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12862-015-0515-x) contains supplementary material, which is available to authorized users. BioMed Central 2015-10-28 /pmc/articles/PMC4625875/ /pubmed/26511837 http://dx.doi.org/10.1186/s12862-015-0515-x Text en © Hermansen et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Hermansen, Russell A.
Mannakee, Brian K.
Knecht, Wolfgang
Liberles, David A.
Gutenkunst, Ryan N.
Characterizing selective pressures on the pathway for de novo biosynthesis of pyrimidines in yeast
title Characterizing selective pressures on the pathway for de novo biosynthesis of pyrimidines in yeast
title_full Characterizing selective pressures on the pathway for de novo biosynthesis of pyrimidines in yeast
title_fullStr Characterizing selective pressures on the pathway for de novo biosynthesis of pyrimidines in yeast
title_full_unstemmed Characterizing selective pressures on the pathway for de novo biosynthesis of pyrimidines in yeast
title_short Characterizing selective pressures on the pathway for de novo biosynthesis of pyrimidines in yeast
title_sort characterizing selective pressures on the pathway for de novo biosynthesis of pyrimidines in yeast
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4625875/
https://www.ncbi.nlm.nih.gov/pubmed/26511837
http://dx.doi.org/10.1186/s12862-015-0515-x
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