For millennia, inhabitants dwelling in the elevated regions of the Argentinian Andes have subsisted on a water source that would prove incapacitating, if not fatal, to the vast majority of people.
Within this locale, pervasive naturally occurring arsenic, originating from volcanic bedrock, infiltrates the subterranean water reserves, thereby contaminating the local potable water supply with concentrations of this noxious metalloid that would present significant health hazards to most human populations.
However, for a specific demographic situated in northern Argentina, the inexorable force of natural selection might have bestowed an unusual genetic endowment.
Based on an exhaustive DNA analysis of individuals across western South America, a community in the Argentinian Andes possesses a gene variant that seemingly facilitates a more secure metabolic processing of arsenic.
“Genomic transformations are a consequence of evolutionary adaptation; however, empirical evidence of distinct human adaptations remains rather scarce,” remarked a research consortium, spearheaded by evolutionary biologists Carina Schlebusch and Lucie Gattepaille from Uppsala University, in a 2015 publication.
“Our findings indicate that adaptation to contend with the environmental stressor arsenic has likely precipitated an escalation in the prevalence of protective variants of AS3MT, thereby furnishing the inaugural substantiation of human acclimatization to a deleterious chemical agent.”
Given sufficient temporal duration and a gradual introduction to a threat, life has demonstrated an extraordinary capacity to adjust to a myriad of extreme environmental circumstances – ranging from scorching temperatures and oxygen deprivation to perilous radiation levels.
Nevertheless, a comparatively limited understanding exists regarding the mechanisms by which human populations acclimate to toxicological agents within their habitat. Arsenic is profoundly toxic, intricately linked to oncogenesis, dermatological abnormalities, congenital malformations, and premature mortality. Furthermore, its prevalence is widespread, being intrinsically present in elevated concentrations within the groundwater of numerous global locales.
The current benchmark for arsenic in potable water, established by the World Health Organization, is set at 10 micrograms per liter.
Prior to the implementation of a filtration system in 2012, the isolated, high-altitude township of San Antonio de los Cobres, located on Argentina’s Puna de Atacama plateau, received drinking water containing approximately 200 micrograms of arsenic per liter – roughly twentyfold the stipulated permissible limit.
Notwithstanding this, the region has been continuously populated for millennia – a minimum of 7,000 years, and potentially as far back as 11,000 years.
This discernible capacity to withstand dangerously elevated arsenic concentrations has perplexed the scientific community for several decades. In 1995, researchers observed that women originating from the Argentinian Andes exhibited a “singular” aptitude for metabolizing arsenic, as evidenced by the presence of specific metabolites in their urine.
Upon entering the organism, arsenic undergoes enzymatic transformation through a series of biochemical pathways. One of these intermediate compounds, known as monomethylated arsenic (MMA), is particularly virulent. A subsequent metabolite, dimethylated arsenic (DMA), is more readily eliminated by the body via urinary excretion.
Individuals residing in San Antonio de los Cobres exhibited a propensity to generate diminished quantities of the toxic intermediate and greater proportions of the readily excretable form, thereby suggesting an exceptional metabolic efficiency in processing arsenic.
Motivated by this discovery, Schlebusch, Gattepaille, and their associates embarked on a quest to elucidate the underlying genetic mechanisms.
The research team procured genetic material from 124 women in San Antonio de los Cobres through buccal swabs, whose urinary analyses had previously revealed the same arsenic metabolite profile as observed in the 1995 investigation. Subsequently, they conducted an extensive analysis of millions of genetic markers across the entire genome.
To ascertain whether the identified gene variant held exclusivity to the Argentine populace, the researchers juxtaposed their findings with publicly accessible genomic data from Peru and Colombia, derived from the international 1000 Genomes Project.
Priors studies had posited that an enzyme designated as arsenic (+3 oxidation state) methyltransferase (AS3MT) could play a pivotal role in arsenic metabolism, thus becoming the focal point of their investigative efforts.
Their investigation uncovered a localized cluster of genetic variations in proximity to the AS3MT gene that exerted a significant influence on the body’s arsenic processing capabilities. These variants were demonstrably more prevalent among individuals from San Antonio de los Cobres when contrasted with genetically proximate populations in Peru and Colombia.
These variants appear to augment the body’s efficacy in converting arsenic into forms amenable to safe urinary excretion, thereby mitigating the accumulation of the most cytotoxic intermediate compounds – a conclusion that harmonizes precisely with earlier epidemiological analyses of urinary arsenic metabolites.
While arsenic contamination is a pervasive global issue, remarkably few communities have endured such protracted periods of intense exposure.
In San Antonio de los Cobres, the inhabitants have coexisted with arsenic in their groundwater for millennia – an ample duration for natural selection to preferentially cultivate traits that attenuate susceptibility to arsenic’s deleterious effects.
Subsequent investigations suggest that analogous genetic markers might also manifest in other Andean communities having undergone generational exposure to arsenic, lending credence to the assertion that long-term exposure can indeed instigate genetic resilience and suggesting that this adaptive trait might be more widely distributed throughout the region.
“Considering the severe detrimental health consequences of arsenic exposure on both pediatric and adult populations,” the researchers articulated, “individuals bearing the arsenic-tolerance haplotype… would likely possess a profound selective advantage within environments characterized by high arsenic concentrations.”
This groundbreaking research was formally published in Molecular Biology and Evolution.
