Roca-Umbert Würth, AnaCaro Consuegra, RocioLondono-Correa, DiegoRodriguez-Lozano, Gabriel FelipeVicente García, Rubén, 1978-Bosch Fusté, Elena2022-04-252022-04-252022Roca-Umbert A, Caro-Consuegra R, Londono-Correa D, Rodriguez-Lozano GF, Vicente R, Bosch E. Understanding signatures of positive natural selection in human zinc transporter genes. Sci Rep. 2022 Mar 12;12(1):4320. DOI: 10.1038/s41598-022-08439-y2045-2322http://hdl.handle.net/10230/52882Zinc is an essential micronutrient with a tightly regulated systemic and cellular homeostasis. In humans, some zinc transporter genes (ZTGs) have been previously reported as candidates for strong geographically restricted selective sweeps. However, since zinc homeostasis is maintained by the joint action of 24 ZTGs, other more subtle modes of selection could have also facilitated human adaptation to zinc availability. Here, we studied whether the complete set of ZTGs are enriched for signals of positive selection in worldwide populations and population groups from South Asia. ZTGs showed higher levels of genetic differentiation between African and non-African populations than would be randomly expected, as well as other signals of polygenic selection outside Africa. Moreover, in several South Asian population groups, ZTGs were significantly enriched for SNPs with unusually extended haplotypes and displayed SNP genotype-environmental correlations when considering zinc deficiency levels in soil in that geographical area. Our study replicated some well-characterized targets for positive selection in East Asia and sub-Saharan Africa, and proposes new candidates for follow-up in South Asia (SLC39A5) and Africa (SLC39A7). Finally, we identified candidate variants for adaptation in ZTGs that could contribute to different disease susceptibilities and zinc-related human health traits.application/pdfeng© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41598-022-08439-yEvolutionEvolutionary biologyEvolutionary geneticsGenetic variationPopulation geneticsinfo:eu-repo/semantics/openAccess