Human adaptation to arsenic in Bolivians living in the Andes

Jessica De Loma, Mário Vicente, Noemi Tirado, Franz Ascui, Marie Vahter, Jacques Gardon, Carina M. Schlebusch, Karin Broberg

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Humans living in the Andes Mountains have been historically exposed to arsenic from natural sources, including drinking water. Enzymatic methylation of arsenic allows it to be excreted more efficiently by the human body. Adaptation to high-arsenic environments via enhanced methylation and excretion of arsenic was first reported in indigenous women in the Argentinean Andes, but whether adaptation to arsenic is a general phenomenon across native populations from the Andes Mountains remains unclear. Therefore, we evaluated whether adaptation to arsenic has occurred in the Bolivian Andes by studying indigenous groups who belong to the Aymara-Quechua and Uru ethnicities and have lived in the Bolivian Andes for generations. Our population genetics methods, including genome-wide selection scans based on linkage disequilibrium patterns and allele frequency differences, in combination with targeted and whole-genome sequencing and genotype–phenotype association analyses, detected signatures of positive selection near the gene encoding arsenite methyltransferase (AS3MT), the main arsenic methylating enzyme. This was among the strongest selection signals (top 0.5% signals via locus-specific branch length and extended haplotype homozygosity tests) at a genome-wide level in the Bolivian study groups. We found a large haplotype block of 676 kb in the AS3MT region and identified candidate functional variants for further analysis. Moreover, our analyses revealed associations between AS3MT variants and the fraction of mono-methylated arsenic in urine and showed that the Bolivian study groups had the highest frequency of alleles associated with more efficient arsenic metabolism reported so far. Our data support the idea that arsenic exposure has been a driver for human adaptation to tolerate arsenic through more efficient arsenic detoxification in different Andean populations.

Original languageEnglish
Article number134764
JournalChemosphere
Volume301
DOIs
StatePublished - Aug 2022

Bibliographical note

Funding Information:
This work was supported by HydroSciences laboratory (IRD-University of Montpellier, France), the Eric Philip S?rensens Stiftelse (Sweden), the Swedish Research Council (2016?05799 and 2017?01239), Karolinska Institutet (Sweden), the Swedish International Development Cooperation Agency, and the Genetics Institute at Universidad Mayor de San Andr?s (Bolivia). In addition, CS was funded by the European Research Council (ERC StG AfricanNeo, grant no. 759933). The SNP&SEQ Technology Platform and the Uppsala Genome Center are supported by the Swedish Research Council for Infrastructures and Science for Life Laboratory (Sweden). The SNP&SEQ Technology Platform is also supported by the Knut and Alice Wallenberg Foundation.

Funding Information:
This work was supported by HydroSciences laboratory (IRD- University of Montpellier , France), the Eric Philip Sörensens Stiftelse (Sweden), the Swedish Research Council ( 2016–05799 and 2017–01239 ), Karolinska Institutet (Sweden), the Swedish International Development Cooperation Agency, and the Genetics Institute at Universidad Mayor de San Andrés (Bolivia). In addition, CS was funded by the European Research Council (ERC StG AfricanNeo, grant no. 759933 ). The SNP&SEQ Technology Platform and the Uppsala Genome Center are supported by the Swedish Research Council for Infrastructures and Science for Life Laboratory (Sweden). The SNP&SEQ Technology Platform is also supported by the Knut and Alice Wallenberg Foundation .

Publisher Copyright:
© 2022 The Authors

Keywords

  • AS3MT
  • Drinking water
  • Evolution
  • Selection
  • Tolerance
  • Toxic

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