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Distribution of events of positive selection and population differentiation in a metabolic pathway: the case of asparagine N-glycosylation

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dc.contributor.author Dall'Olio, Giovanni Marco, 1983-
dc.contributor.author Laayouni, Hafid, 1968-
dc.contributor.author Luisi, Pierre, 1985-
dc.contributor.author Sikora, Martin, 1976-
dc.contributor.author Montanucci, Ludovica, 1978-
dc.contributor.author Bertranpetit, Jaume, 1952-
dc.date.accessioned 2013-11-28T11:32:11Z
dc.date.available 2013-11-28T11:32:11Z
dc.date.issued 2012
dc.identifier.citation Dall'Olio GM, Laayouni H, Luisi P, Sikora M, Montanucci L, Bertranpetit J. Distribution of events of positive selection and population differentiation in a metabolic pathway: the case of asparagine N-glycosylation. BMC Evol. Biol. 2012;12(1):98. DOI: 10.1186/1471-2148-12-98
dc.identifier.issn 1471-2148
dc.identifier.uri http://hdl.handle.net/10230/21310
dc.description.abstract Asparagine N-Glycosylation is one of the most important forms of protein post-translational modification in eukaryotes. This metabolic pathway can be subdivided into two parts: an upstream sub-pathway required for achieving proper folding for most of the proteins synthesized in the secretory pathway, and a downstream sub-pathway required to give variability to trans-membrane proteins, and involved in adaptation to the environment and innate immunity. Here we analyze the nucleotide variability of the genes of this pathway in human populations, identifying which genes show greater population differentiation and which genes show signatures of recent positive selection. We also compare how these signals are distributed between the upstream and the downstream parts of the pathway, with the aim of exploring how forces of population differentiation and positive selection vary among genes involved in the same metabolic pathway but subject to different functional constraints. Our results show that genes in the downstream part of the pathway are more likely to show a signature of population differentiation, while events of positive selection are equally distributed among the two parts of the pathway. Moreover, events of positive selection are frequent on genes that are known to be at bifurcation points, and that are identified as being in key position by a network-level analysis such as MGAT3 and GCS1. These findings indicate that the upstream part of the Asparagine N-Glycosylation pathway has lower diversity among populations, while the downstream part is freer to tolerate diversity among populations. Moreover, the distribution of signatures of population differentiation and positive selection can change between parts of a pathway, especially between parts that are exposed to different functional constraints. Our results support the hypothesis that genes involved in constitutive processes can be expected to show lower population differentiation, while genes involved in traits related to the environment should show higher variability. Taken together, this work broadens our knowledge on how events of population differentiation and of positive selection are distributed among different parts of a metabolic pathway.
dc.description.sponsorship This work was funded by grant BFU2010-19443 (subprogram BMC) awarded to JB by Ministerio de Ciencia y Tecnología (Spain), and the Direcció General de Recerca, Generalitat de Catalunya (Grup de Recerca Consolidat 2009 SGR 1101). GMD is supported by a FPI fellowship (BES-2009-017731) from the Ministerio de Ciencia y Tecnología, (Spain). PL is supported by a PhD fellowship from “Acción Estratégica de Salud, 2008-2011” from Instituto de Salud Carlos III and LM is supported by a postdoctoral fellowship from the Juan de la Cierva Program of the Spanish Ministry of Science and Innovation (MICINN).
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher BioMed Central
dc.relation.ispartof BMC Evol. Biol. 2012;12(1):98
dc.rights © Dall'Olio et al. Creative Commons Attribution License
dc.rights.uri http://creativecommons.org/licenses/by/2.0/
dc.subject.other Genètica de poblacions humanes
dc.subject.other Genètica evolutiva
dc.title Distribution of events of positive selection and population differentiation in a metabolic pathway: the case of asparagine N-glycosylation
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1186/1471-2148-12-98
dc.subject.keyword Homo sapiens
dc.subject.keyword Positive selection
dc.subject.keyword Population differentiation
dc.subject.keyword Asparagine N-Glycosylation
dc.subject.keyword Glycosylation
dc.subject.keyword Pathway analysis
dc.subject.keyword Calnexin/calreticulin cycle,
dc.subject.keyword Adaptation to environment
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2010-19443
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BES2009-017731
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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