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Gene connectivity and enzyme evolution in the human metabolic network
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 a...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724310/ https://www.ncbi.nlm.nih.gov/pubmed/31481097 http://dx.doi.org/10.1186/s13062-019-0248-7 |
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author | Dobon, Begoña Montanucci, Ludovica Peretó, Juli Bertranpetit, Jaume Laayouni, Hafid |
author_facet | Dobon, Begoña Montanucci, Ludovica Peretó, Juli Bertranpetit, Jaume Laayouni, Hafid |
author_sort | Dobon, Begoña |
collection | PubMed |
description | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13062-019-0248-7) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6724310 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-67243102019-09-10 Gene connectivity and enzyme evolution in the human metabolic network Dobon, Begoña Montanucci, Ludovica Peretó, Juli Bertranpetit, Jaume Laayouni, Hafid Biol Direct Research 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13062-019-0248-7) contains supplementary material, which is available to authorized users. BioMed Central 2019-09-03 /pmc/articles/PMC6724310/ /pubmed/31481097 http://dx.doi.org/10.1186/s13062-019-0248-7 Text en © The Author(s). 2019 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 Dobon, Begoña Montanucci, Ludovica Peretó, Juli Bertranpetit, Jaume Laayouni, Hafid Gene connectivity and enzyme evolution in the human metabolic network |
title | Gene connectivity and enzyme evolution in the human metabolic network |
title_full | Gene connectivity and enzyme evolution in the human metabolic network |
title_fullStr | Gene connectivity and enzyme evolution in the human metabolic network |
title_full_unstemmed | Gene connectivity and enzyme evolution in the human metabolic network |
title_short | Gene connectivity and enzyme evolution in the human metabolic network |
title_sort | gene connectivity and enzyme evolution in the human metabolic network |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724310/ https://www.ncbi.nlm.nih.gov/pubmed/31481097 http://dx.doi.org/10.1186/s13062-019-0248-7 |
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