Human evolution and arsenic detoxification

Carina Schlebusch and colleagues just published an article in Molecular Biology and Evolution demonstrating human adaptation to the locally high arsenic levels in groundwater in the Argentine Andes. This work is the first to show a genetic adaptation that allows the detoxification of a environmental toxin (arsenic) in humans.

Title: Human adaptation to arsenic-rich environments

Abstract: “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 (F_ST = 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.”

Take home message: Natural selection has acted powerfully to produce genetic change and human adaptation on relatively short time scales (since between 7,000 to 11,000 years ago). These results fit in nicely with the proposal of Marlene Zuk, the author of Paleofantasy, that humans, like other organisms, can evolve relatively quickly when conditions change and impose selection. Turns out the genetic capacity to detoxify arsenic joins other human genetic traits e.g. digestion of milk lactose and adaptation to high altitude hypoxia that have evolved in the last few thousand years.

References:

Schlebusch CM, Gattepaille LM, Engström K, Vahter M, Jakobsson M, Broberg K. Human Adaptation to Arsenic-Rich Environments. Mol Biol Evol. 2015 Mar 3. pii: msv046. PMID: 25739736

Zuk M. 2013. Paleofantasy: What Evolution Really Tells Us About Sex, Diet, and How We Live. New York, NY: WW Norton & Company

Tishkoff S. et al. Convergent adaptation of human lactase persistence in Africa and Europe. Nat Genet. 2007 Jan;39(1):31-40. Epub 2006 Dec 10.

Beall C. Two routes to functional adaptation: Tibetan and Andean high-altitude natives. PNAS May 15, vol. 104, 1