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In Vitro Scratch Assay to Demonstrate Effects of Arsenic on Skin Cell Migration
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Human adaptation to arsenic-rich environments.

Carina M Schlebusch1, Lucie M Gattepaille1, Karin Engström2

  • 1Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden mattias.jakobsson@ebc.uu.se karin.broberg@ki.se.

Molecular Biology and Evolution
|March 6, 2015
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Human populations in the Argentinean Andes show unique arsenic metabolism due to adaptation. Genetic analysis reveals the AS3MT gene is key to this adaptation, offering the first evidence of human adaptation to toxic chemicals.

Keywords:
AS3MTselectiontoxic

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Area of Science:

  • Human genetics
  • Environmental toxicology
  • Human adaptation

Background:

  • Human adaptation to environmental stressors is a key area of study.
  • Evidence for specific human adaptations, particularly to toxic substances, is limited.
  • Arsenic contamination in drinking water poses a significant health risk in some regions.

Purpose of the Study:

  • To investigate the genetic basis of arsenic metabolism and adaptation in humans.
  • To identify specific genes associated with arsenic tolerance in populations exposed to high environmental arsenic levels.
  • To provide evidence for human adaptation to toxic chemical exposure.

Main Methods:

  • Genotyping of over 4.3 million single nucleotide polymorphisms (SNPs) in women from the Argentinean Andes.
  • Analysis of arsenic metabolism through urine metabolite measurements (monomethylated and dimethylated arsenic).
  • Population genetic analyses including FST, Locus-Specific Branch Length, and extended haplotype homozygosity.

Main Results:

  • A strong association was found between the AS3MT gene and arsenic metabolism in the Argentinean Andes population.
  • Significant genetic differentiation around the AS3MT gene was observed compared to a Peruvian population with lower arsenic exposure.
  • Evidence of a selective sweep around AS3MT in the Argentinean Andes population suggests adaptive evolution.

Conclusions:

  • The AS3MT gene plays a major role in human arsenic metabolism and adaptation.
  • This study provides the first evidence of human adaptation to a toxic chemical, specifically arsenic, driven by increased frequencies of protective AS3MT variants.
  • Environmental arsenic exposure has likely driven the selection of beneficial genetic variants in high-altitude Andean populations.