Human Adaptation to Arsenic Uncovered in Argentinian Andes
For thousands of years, humans in the Argentinian Andes have consumed water containing naturally occurring arsenic at levels significantly exceeding recommended limits. A population in northern Argentina exhibits a genetic variant that likely assists in the safer metabolism of arsenic.
A DNA analysis across western South America identified a specific gene variant within this Argentinian Andean population, suggesting an adaptation to tolerate the environmental stressor arsenic. This constitutes initial evidence of human adaptation to a toxic chemical.
This study provides initial evidence of human adaptation to a toxic chemical, revealing a specific gene variant in an Argentinian Andean population that aids in arsenic tolerance.
Centuries of Exposure in the Puna de Atacama
Arsenic is a highly toxic metalloid associated with conditions such as cancer, skin lesions, birth defects, and premature death. The World Health Organization recommends a limit of 10 micrograms per liter for arsenic in drinking water.
Prior to 2012, the town of San Antonio de los Cobres, located in Argentina's Puna de Atacama plateau, had drinking water containing approximately 200 micrograms of arsenic per liter. This level is 20 times the recommended limit. The region has been inhabited for at least 7,000 years, and potentially up to 11,000 years.
Understanding Arsenic Metabolism
Previous observations in 1995 indicated that women from the Argentinian Andes possessed a unique capacity to metabolize arsenic, evidenced by metabolite profiles in their urine. When arsenic enters the body, enzymes convert it through various chemical forms. An intermediate form, monomethylated arsenic (MMA), is particularly toxic, while dimethylated arsenic (DMA) is more readily excreted.
Individuals in San Antonio de los Cobres tended to produce less toxic intermediate MMA and more excretable DMA, suggesting enhanced efficiency in arsenic processing.
Genetic Investigation Pinpoints Key Variant
Researchers, led by evolutionary biologists Carina Schlebusch and Lucie Gattepaille, investigated this unique metabolic capacity at the genetic level. The team collected DNA samples from 124 women in San Antonio de los Cobres and analyzed millions of genetic markers. They compared these results with publicly available genome data from Peru and Colombia. Their focus was on the arsenic (+3 oxidation state) methyltransferase (AS3MT) enzyme, known to be crucial in arsenic metabolism.
The AS3MT Gene and Enhanced Metabolism
They identified a cluster of genetic variants near the AS3MT gene that significantly influenced arsenic processing. These variants were substantially more prevalent in the San Antonio de los Cobres population compared to genetically similar groups in Peru and Colombia.
The variants appear to enhance the body's efficiency in converting arsenic into forms that can be safely excreted, thus reducing the accumulation of highly toxic intermediate compounds.
Natural Selection at Play
Long-term exposure to high arsenic levels, as experienced by the San Antonio de los Cobres population for thousands of years, likely led to natural selection favoring traits that reduce vulnerability to arsenic's toxic effects. Subsequent research suggests similar genetic signals may exist in other Andean populations with generational arsenic exposure, indicating this adaptation could be more widespread.
Researchers concluded that individuals possessing the arsenic-tolerance haplotype would have a strong selective advantage in environments with high arsenic concentrations, given the severe health implications of arsenic.