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dc.contributor.authorMartínez Cadenas, Conrado
dc.contributor.authorLópez, Saioa
dc.contributor.authorRibas, Gloria
dc.contributor.authorFlores, Carlos
dc.contributor.authorGarcía, Oscar
dc.contributor.authorSevilla, Arrate
dc.contributor.authorSmith-Zubiaga, I.
dc.contributor.authorIbarrola-Villava, Maider
dc.contributor.authorPino-Yanes, M .
dc.contributor.authorGardeazabal, Jesús
dc.contributor.authorBoyano, Dolores
dc.contributor.authorGarcía de Galdeano, Alicia
dc.contributor.authorIzagirre, Neskuts
dc.contributor.authorde la Rúa, Concepción
dc.contributor.authorAlonso, Santos
dc.date.accessioned2014-06-13T07:39:52Z
dc.date.available2014-06-13T07:39:52Z
dc.date.issued2013
dc.identifier.citationMARTÍNEZ-CADENAS, Conrado, et al. Simultaneous purifying selection on the ancestral MC1R allele and positive selection on the melanoma-risk allele V60L in South Europeans. Molecular biology and evolution, 2013, vol. 30, no 12, p. 2654-2665.ca_CA
dc.identifier.issn0737-4038
dc.identifier.issn1537-1719
dc.identifier.urihttp://hdl.handle.net/10234/94790
dc.description.abstractIn humans, the geographical apportionment of the coding diversity of the pigmentary locus melanocortin-1 receptor (MC1R) is, unusually, higher in Eurasians than in Africans. This atypical observation has been interpreted as the result of purifying selection due to functional constraint on MC1R in high UV-B radiation environments. By analyzing 3,142 human MC1R alleles from different regions of Spain in the context of additional haplotypic information from the 1000 Genomes (1000G) Project data, we show that purifying selection is also strong in southern Europe, but not so in northern Europe. Furthermore, we show that purifying and positive selection act simultaneously on MC1R. Thus, at least in Spain, regions at opposite ends of the incident UV-B radiation distribution show significantly different frequencies for the melanoma-risk allele V60L (a mutation also associated to red hair and fair skin and even blonde hair), with higher frequency of V60L at those regions of lower incident UV-B radiation. Besides, using the 1000G south European data, we show that the V60L haplogroup is also characterized by an extended haplotype homozygosity (EHH) pattern indicative of positive selection. We, thus, provide evidence for an adaptive value of human skin depigmentation in Europe and illustrate how an adaptive process can simultaneously help to maintain a disease-risk allele. In addition, our data support the hypothesis proposed by Jablonski and Chaplin (Human skin pigmentation as an adaptation to UVB radiation. Proc Natl Acad Sci U S A. 2010;107:8962-8968), which posits that habitation of middle latitudes involved the evolution of partially depigmented phenotypes that are still capable of suitable tanning.ca_CA
dc.description.sponsorShipThis works was supported by the former Spanish Ministerio de Ciencia e Innovación, project CGL2008-04066/BOS to S.A.; by the Dpt. Educacion, Universidades e Investigación of the Basque Government, project IT542-10; by program UFI11/09 by the University of the Basque Country, by "Programa de Investigacion Cientifica de la Universidad de La Laguna" (boc-a- 2010-255-7177), and by grants from the Health Institute “Carlos III” (FIS PI08/1383, FIS PI11/00623) to C.F. and co-financed by the European Regional Development Funds, “A way of making Europe” from the European Union. M.P.Y. was supported by a postdoctoral fellowship from Fundación Ramón Areces. We thank the Spanish Banco Nacional de AND (BNADN) (http://www.bancoadn.org/) for providing us with DNA samples from all over Spain. We also thank the Spanish Agencia Estatal de Meteorología (AEMET) (http://www.aemet.es/) for kindly providing us with the UV-B radiation data.ca_CA
dc.format.extent12 p.ca_CA
dc.format.mimetypeapplication/pdfca_CA
dc.language.isoengca_CA
dc.publisherOxford University Pressca_CA
dc.relation.isPartOfMolecular biology and evolution (2013) vol. 30, no 12,ca_CA
dc.rightsCopyright © Society for Molecular Biology and Evolutionca_CA
dc.subjectSkin pigmentationca_CA
dc.subjectMC1Rca_CA
dc.subjectAdaptive evolutionca_CA
dc.subjectMelanomaca_CA
dc.titleSimultaneous purifying selection on the ancestral MC1R allele and positive selection on the melanoma-risk allele V60L in South Europeansca_CA
dc.typeinfo:eu-repo/semantics/articleca_CA
dc.identifier.doihttp://dx.doi.org/10.1093/molbev/mst158
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessca_CA
dc.relation.publisherVersionhttp://mbe.oxfordjournals.org/content/early/2013/09/12/molbev.mst158.abstract#aff-1ca_CA


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