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Gene connectivity and enzyme evolution in the human metabolic network

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dc.contributor.author Dobón Berenguer, Begoña, 1987-
dc.contributor.author Montanucci, Ludovica, 1978-
dc.contributor.author Peretó, Juli
dc.contributor.author Bertranpetit, Jaume, 1952-
dc.contributor.author Laayouni, Hafid, 1968-
dc.date.accessioned 2019-10-03T10:37:20Z
dc.date.available 2019-10-03T10:37:20Z
dc.date.issued 2019
dc.identifier.citation Dobon B, Montanucci L, Peretó J, Bertranpetit J, Laayouni H. Gene connectivity and enzyme evolution in the human metabolic network. Biol Direct. 2019;14(1):17. DOI: 10.1186/s13062-019-0248-7
dc.identifier.issn 1745-6150
dc.identifier.uri http://hdl.handle.net/10230/42378
dc.description.abstract Background: Determining the factors involved in the likelihood of a gene being under adaptive selection is still a challenging goal in Evolutionary Biology. Here, we perform an evolutionary analysis of the human metabolic genes to explore the associations between network structure and the presence and strength of natural selection in the genes whose products are involved in metabolism. Purifying and positive selection are estimated at interspecific (among mammals) and intraspecific (among human populations) levels, and the connections between enzymatic reactions are differentiated between incoming (in-degree) and outgoing (out-degree) links. Results: We confirm that purifying selection has been stronger in highly connected genes. Long-term positive selection has targeted poorly connected enzymes, whereas short-term positive selection has targeted different enzymes depending on whether the selective sweep has reached fixation in the population: genes under a complete selective sweep are poorly connected, whereas those under an incomplete selective sweep have high out-degree connectivity. The last steps of pathways are more conserved due to stronger purifying selection, with long-term positive selection targeting preferentially enzymes that catalyze the first steps. However, short-term positive selection has targeted enzymes that catalyze the last steps in the metabolic network. Strong signals of positive selection have been found for metabolic processes involved in lipid transport and membrane fluidity and permeability. Conclusions: Our analysis highlights the importance of analyzing the same biological system at different evolutionary timescales to understand the evolution of metabolic genes and of distinguishing between incoming and outgoing links in a metabolic network. Short-term positive selection has targeted enzymes with a different connectivity profile depending on the completeness of the selective sweep, while long-term positive selection has targeted genes with fewer connections that code for enzymes that catalyze the first steps in the network. Reviewers: This article was reviewed by Diamantis Sellis and Brandon Invergo.
dc.description.sponsorship This study has been possible thanks to grant BFU2016–77961-P (AEI/FEDER, UE) awarded by the Agencia Estatal de Investigación (Ministerio de Ciencia, Innovación y Universidades, Spain) and with the support of Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya (GRC 2017 527 SGR 702) to JB. Part of the “Unidad de Excelencia María de Maeztu” (MDM-2014-0370), funded by the Ministerio de Economía, Industria y Competividad (MINECO, Spain). JP work is supported in part by the Agencia Estatal de Investigación (Ministerio de Ciencia, Innovación y Universidades, Spain) Helios grant reference: BIO2015–66960-C3–1-R (co-financed by FEDER) and by the European Union through the BioRoboost project (H2020-NMBP-TR-IND-2018-2020/BIOTEC-01-2018 (CSA), Project ID 210491758). BD is supported by F.P.U. grant FPU13/06813 from the Ministerio de Educación, Cultura y Deporte (Spain).
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher BioMed Central
dc.relation.ispartof Biology Direct. 2019;14(1):17
dc.rights © The Author(s). 2019 Open Access This 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.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Gene connectivity and enzyme evolution in the human metabolic network
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1186/s13062-019-0248-7
dc.subject.keyword Network topology
dc.subject.keyword Degree
dc.subject.keyword Connectivity
dc.subject.keyword Metabolism
dc.subject.keyword Enzymes
dc.subject.keyword Positive selection
dc.subject.keyword Purifying selection
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2016-77961-P
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BIO2015-66960-C3-1-R
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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