Engelken, JohannesEspadas, GuadalupeMancuso, Francesco M.Bonet, NúriaScherr, Anna-LenaJímenez Álvarez, VictoriaCodina i Solà, Marta, 1988-Medina Stacey, DanielSpataro, Nino, 1984-Stoneking, MarkCalafell i Majó, FrancescSabidó Aguadé, Eduard, 1981-Bosch Fusté, Elena2016-06-072016-06-072016Engelken 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/msv2670737-4038http://hdl.handle.net/10230/26862Essential 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.application/pdfeng© 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.HomeòstasiProteòmicainfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1093/molbev/msv267Micronutrient homeostasisPositive selectionProteomicsQuantitative trait lociTrace elementsinfo:eu-repo/semantics/openAccess