Author, as appears in the article.: 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
Department: Medicina i Cirurgia
URV's Author/s: Muntané Medina, Gerard
Keywords: Positive selection transport complexes roles neanderthal natural-selection mutation introgression genomics family endoplasmic-reticulum
Abstract: 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.
Thematic Areas: 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
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: gerard.muntane@urv.cat
Record's date: 2024-08-03
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1010950
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Plos Genetics. 19 (9): e1010950-e1010950
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
Article's DOI: 10.1371/journal.pgen.1010950
Entity: Universitat Rovira i Virgili
Journal publication year: 2023
Publication Type: Journal Publications