Human adaptation to arsenic-rich environments.
Adaptation drives genomic changes; however, evidence of specific adaptations in humans remains limited. We found that inhabitants of the northern Argentinean Andes, an arid region where elevated arsenic concentrations in available drinking water is common, have unique arsenic metabolism, with efficient methylation and excretion of the major metabolite dimethylated arsenic and a less excretion of the highly toxic monomethylated metabolite. We genotyped women from this population for 4,301,332 single nucleotide polymorphisms (SNPs) and found a strong association between the AS3MT (arsenic [+3 oxidation state] methyltransferase) gene and mono- and dimethylated arsenic in urine, suggesting that AS3MT functions as the major gene for arsenic metabolism in humans. We found strong genetic differentiation around AS3MT in the Argentinean Andes population, compared with a highly related Peruvian population (FST = 0.014) from a region with much less environmental arsenic. Also, 13 of the 100 SNPs with the highest genome-wide Locus-Specific Branch Length occurred near AS3MT. In addition, our examination of extended haplotype homozygosity indicated a selective sweep of the Argentinean Andes population, in contrast to Peruvian and Colombian populations. Our data show that adaptation to tolerate the environmental stressor arsenic has likely driven an increase in the frequencies of protective variants of AS3MT, providing the first evidence of human adaptation to a toxic chemical.
Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden mattias.jakobsson@ebc.uu.se karin.broberg@ki.se.
Carina M
CM
Schlebusch
Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden mattias.jakobsson@ebc.uu.se karin.broberg@ki.se.
Lucie M
LM
Gattepaille
Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
Karin
K
Engström
Unit of Metals and Health, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Marie
M
Vahter
Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden Science for Life Laboratory, Uppsala University, Uppsala, Sweden mattias.jakobsson@ebc.uu.se karin.broberg@ki.se.
Mattias
M
Jakobsson
Unit of Metals and Health, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden mattias.jakobsson@ebc.uu.se karin.broberg@ki.se.
Karin
K
Broberg
D000222:Adaptation, Physiological / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001118:Argentina; D001151:Arsenic / Q000032:analysis* / Q000633:toxicity / Q000652:urine; D030541:Databases, Genetic; D005260:Female; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016014:Linear Models; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D010568:Peru; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D055815:Young Adult
D008780:Methyltransferases; C505756:AS3MT protein, human; D001151:Arsenic
AS3MT; selection; toxic