Articles producció científica> Medicina i Cirurgia

Human genetic adaptation related to cellular zinc homeostasis

  • Datos identificativos

    Identificador: imarina:9330288
    Autores:
    Roca-Umbert, AGarcia-Calleja, JVogel-González, MFierro-Villegas, AIll-Raga, GHerrera-Fernández, VBosnjak, AMuntané, GGutiérrez, ECampelo, FVicente, RBosch, E
    Resumen:
    SLC30A9 encodes a ubiquitously zinc transporter (ZnT9) and has been consistently suggested as a candidate for positive selection in humans. However, no direct adaptive molecular phenotype has been demonstrated. Our results provide evidence for directional selection operating in two major complementary haplotypes in Africa and East Asia. These haplotypes are associated with differential gene expression but also differ in the Met50Val substitution (rs1047626) in ZnT9, which we show is found in homozygosis in the Denisovan genome and displays accompanying signatures suggestive of archaic introgression. Although we found no significant differences in systemic zinc content between individuals with different rs1047626 genotypes, we demonstrate that the expression of the derived isoform (ZnT9 50Val) in HEK293 cells shows a gain of function when compared with the ancestral (ZnT9 50Met) variant. Notably, the ZnT9 50Val variant was found associated with differences in zinc handling by the mitochondria and endoplasmic reticulum, with an impact on mitochondrial metabolism. Given the essential role of the mitochondria in skeletal muscle and since the derived allele at rs1047626 is known to be associated with greater susceptibility to several neuropsychiatric traits, we propose that adaptation to cold may have driven this selection event, while also impacting predisposition to neuropsychiatric disorders in modern humans.Copyright: © 2023 Roca-Umbert et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
  • Otros:

    Autor según el artículo: Roca-Umbert, A; Garcia-Calleja, J; Vogel-González, M; Fierro-Villegas, A; Ill-Raga, G; Herrera-Fernández, V; Bosnjak, A; Muntané, G; Gutiérrez, E; Campelo, F; Vicente, R; Bosch, E
    Departamento: Medicina i Cirurgia
    Autor/es de la URV: Muntané Medina, Gerard
    Palabras clave: Positive selection transport complexes roles neanderthal natural-selection mutation introgression genomics family endoplasmic-reticulum
    Resumen: SLC30A9 encodes a ubiquitously zinc transporter (ZnT9) and has been consistently suggested as a candidate for positive selection in humans. However, no direct adaptive molecular phenotype has been demonstrated. Our results provide evidence for directional selection operating in two major complementary haplotypes in Africa and East Asia. These haplotypes are associated with differential gene expression but also differ in the Met50Val substitution (rs1047626) in ZnT9, which we show is found in homozygosis in the Denisovan genome and displays accompanying signatures suggestive of archaic introgression. Although we found no significant differences in systemic zinc content between individuals with different rs1047626 genotypes, we demonstrate that the expression of the derived isoform (ZnT9 50Val) in HEK293 cells shows a gain of function when compared with the ancestral (ZnT9 50Met) variant. Notably, the ZnT9 50Val variant was found associated with differences in zinc handling by the mitochondria and endoplasmic reticulum, with an impact on mitochondrial metabolism. Given the essential role of the mitochondria in skeletal muscle and since the derived allele at rs1047626 is known to be associated with greater susceptibility to several neuropsychiatric traits, we propose that adaptation to cold may have driven this selection event, while also impacting predisposition to neuropsychiatric disorders in modern humans.Copyright: © 2023 Roca-Umbert et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
    Áreas temáticas: Zootecnia / recursos pesqueiros Saúde coletiva Química Odontología Molecular biology Medicina veterinaria Medicina iii Medicina ii Medicina i Interdisciplinar Geociências Genetics (clinical) Genetics & heredity Genetics Filosofia/teologia:subcomissão filosofia Farmacia Engenharias iv Educação física Ecology, evolution, behavior and systematics Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências agrárias i Ciência da computação Cancer research Biotecnología Biodiversidade Astronomia / física Antropologia / arqueologia
    Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
    Direcció de correo del autor: gerard.muntane@urv.cat
    Fecha de alta del registro: 2024-08-03
    Versión del articulo depositado: info:eu-repo/semantics/publishedVersion
    Enlace a la fuente original: https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1010950
    URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referencia al articulo segun fuente origial: Plos Genetics. 19 (9): e1010950-e1010950
    Referencia de l'ítem segons les normes APA: Roca-Umbert, A; Garcia-Calleja, J; Vogel-González, M; Fierro-Villegas, A; Ill-Raga, G; Herrera-Fernández, V; Bosnjak, A; Muntané, G; Gutiérrez, E; Cam (2023). Human genetic adaptation related to cellular zinc homeostasis. Plos Genetics, 19(9), e1010950-e1010950. DOI: 10.1371/journal.pgen.1010950
    DOI del artículo: 10.1371/journal.pgen.1010950
    Entidad: Universitat Rovira i Virgili
    Año de publicación de la revista: 2023
    Tipo de publicación: Journal Publications
  • Palabras clave:

    Cancer Research,Ecology, Evolution, Behavior and Systematics,Genetics,Genetics & Heredity,Genetics (Clinical),Molecular Biology
    Positive selection
    transport complexes
    roles
    neanderthal
    natural-selection
    mutation
    introgression
    genomics
    family
    endoplasmic-reticulum
    Zootecnia / recursos pesqueiros
    Saúde coletiva
    Química
    Odontología
    Molecular biology
    Medicina veterinaria
    Medicina iii
    Medicina ii
    Medicina i
    Interdisciplinar
    Geociências
    Genetics (clinical)
    Genetics & heredity
    Genetics
    Filosofia/teologia:subcomissão filosofia
    Farmacia
    Engenharias iv
    Educação física
    Ecology, evolution, behavior and systematics
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Ciências agrárias i
    Ciência da computação
    Cancer research
    Biotecnología
    Biodiversidade
    Astronomia / física
    Antropologia / arqueologia
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