Signatures of evolutionary adaptation in quantitative trait loci influencing trace element homeostasis in liver

Engelken, Johannes; Espadas, Guadalupe; Mancuso, Francesco M.; Bonet, Núria; Scherr, Anna-Lena; Jímenez Álvarez, Victoria; Codina i Solà, Marta, 1988-; Medina Stacey, Daniel; Spataro, Nino, 1984-; Stoneking, Mark; Calafell i Majó, Francesc; Sabidó Aguadé, Eduard, 1981-; Bosch Fusté, Elena

Signatures of evolutionary adaptation in quantitative trait loci influencing trace element homeostasis in liver

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dc.contributor.author Engelken, Johannesca
dc.contributor.author Espadas, Guadalupeca
dc.contributor.author Mancuso, Francesco M.ca
dc.contributor.author Bonet, Núriaca
dc.contributor.author Scherr, Anna-Lenaca
dc.contributor.author Jímenez Álvarez, Victoriaca
dc.contributor.author Codina i Solà, Marta, 1988-ca
dc.contributor.author Medina Stacey, Danielca
dc.contributor.author Spataro, Nino, 1984-ca
dc.contributor.author Stoneking, Markca
dc.contributor.author Calafell i Majó, Francescca
dc.contributor.author Sabidó Aguadé, Eduard, 1981-ca
dc.contributor.author Bosch Fusté, Elenaca
dc.date.accessioned 2016-06-07T14:43:50Z
dc.date.available 2016-06-07T14:43:50Z
dc.date.issued 2016
dc.description.abstract Essential trace elements possess vital functions at molecular, cellular, and physiological levels in health and disease, and they are tightly regulated in the human body. In order to assess variability and potential adaptive evolution of trace element homeostasis, we quantified 18 trace elements in 150 liver samples, together with the expression levels of 90 genes and abundances of 40 proteins involved in their homeostasis. Additionally, we genotyped 169 single nucleotide polymorphism (SNPs) in the same sample set. We detected significant associations for 8 protein quantitative trait loci (pQTL), 10 expression quantitative trait loci (eQTLs), and 15 micronutrient quantitative trait loci (nutriQTL). Six of these exceeded the false discovery rate cutoff and were related to essential trace elements: 1) one pQTL for GPX2 (rs10133290); 2) two previously described eQTLs for HFE (rs12346) and SELO (rs4838862) expression; and 3) three nutriQTLs: The pathogenic C282Y mutation at HFE affecting iron (rs1800562), and two SNPs within several clustered metallothionein genes determining selenium concentration (rs1811322 and rs904773). Within the complete set of significant QTLs (which involved 30 SNPs and 20 gene regions), we identified 12 SNPs with extreme patterns of population differentiation (FST values in the top 5% percentile in at least one HapMap population pair) and significant evidence for selective sweeps involving QTLs at GPX1, SELENBP1, GPX3, SLC30A9, and SLC39A8. Overall, this detailed study of various molecular phenotypes illustrates the role of regulatory variants in explaining differences in trace element homeostasis among populations and in the human adaptive response to environmental pressures related to micronutrients.ca
dc.description.sponsorship This work was supported by Ministerio de Ciencia e Innovación, Spain (grants BFU2008-01046 and SAF2011-29239) and by Direcció General de Recerca, Generalitat de Catalunya (2009SGR-1101 and 2014SGR-866). The CRG/UPF Proteomics Unit is part of the “Plataforma de Recursos Biomoleculares y Bioinformáticos (ProteoRed)” supported by grant PT13/0001 of the Instituto de Salud Carlos III (ISCIII). J.E. was supported by a Postdoctoral scholarship from the Volkswagenstiftung (Az: I/85 198).
dc.format.mimetype application/pdfca
dc.identifier.citation Engelken J, Espadas G, Mancuso FM, Bonet N, Scherr AL, Jímenez-Álvarez V et al. Signatures of evolutionary adaptation in quantitative trait loci influencing trace element homeostasis in liver. Molecular biology and evolution. 2016;33(3):738-54. DOI: 10.1093/molbev/msv267ca
dc.identifier.doi http://dx.doi.org/10.1093/molbev/msv267
dc.identifier.issn 0737-4038
dc.identifier.uri http://hdl.handle.net/10230/26862
dc.language.iso engca
dc.publisher Oxford University Pressca
dc.relation.ispartof Molecular biology and evolution. 2016;33(3):738-54
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2008-01046
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2011-29239
dc.rights © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution./nThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.ca
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/ca
dc.subject.keyword Micronutrient homeostasis
dc.subject.keyword Positive selection
dc.subject.keyword Proteomics
dc.subject.keyword Quantitative trait loci
dc.subject.keyword Trace elements
dc.subject.other Homeòstasica
dc.subject.other Proteòmicaca
dc.title Signatures of evolutionary adaptation in quantitative trait loci influencing trace element homeostasis in liverca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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