For thousands of years, human communities have survived in the Andes by consuming water with arsenic levels up to 20 times higher than recommended levels. by the World Health Organization. Today, science is beginning to understand how its biology changed.
In San Antonio de los Cobres, in the highlands of northwestern Argentina, at more than 3,700 meters above sea level, the water contained nearly 200 micrograms of arsenic per liter before the installation of a filtration system in 2012. The recommended safe limit is just 10. And yet, this region has been inhabited for at least 7,000 years, possibly as long as 11,000. What in any other context would be an extreme risk—chronic exposure to arsenic is associated with cancer, congenital malformations, and premature death—there became an everyday condition.
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The key is how the body processes this element. When arsenic enters the body, it is transformed into different chemical forms. Some are especially dangerous, such as the monomethylated compound (MMA), while others, such as the dimethylated compound (DMA), They can be eliminated more easily through urine. In most people, metabolism generates relatively large amounts of the most toxic compound before reaching its eliminable form. But in this population something different happens.
In the mid-1990s, researchers detected an unusual pattern in women in this region in which their bodies produced less of the most harmful derivative and moved more efficiently toward the form that the body can expel. For years, this ability remained a biochemical oddity. Until genetics offered a possible answer.
In 2015, a team from Uppsala University, led by evolutionary biologists Carina Schlebusch and Lucie Gattepaille analyzed the DNA of 124 women from San Antonio de los Cobres and compared it with populations from Peru and Colombia. They found specific variants around the AS3MT gene—key in arsenic metabolism—that were strongly associated with more efficient processing of the metalloid. These variants were much more frequent in the Argentine population than in other regions with less environmental exposure.
The discovery was accompanied by an even more revealing signal: a “selective sweep.” That is, the genetic footprint left by natural selection when it quickly favors a trait useful for survival. In simple terms, those who metabolized arsenic better were more likely to survive and pass on that advantage. Over time, those variants became predominant.
“Adaptation to tolerate arsenic as an environmental stressor has likely driven an increase in the frequency of protective AS3MT variants,” the team wrote in their study, calling the finding “the first evidence of human adaptation to a toxic chemical.”
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Far from being an isolated case, subsequent research suggests that this type of adaptation could have occurred in parallel in other Andean regions. A study published in 2022 in Chemosphere found similar signals in indigenous populations of Bolivia, where alleles associated with efficient arsenic metabolism reached the highest frequencies recorded so far. Environmental pressure, sustained for generations, would have pushed different communities towards similar evolutionary solutions.
But evolution doesn’t always involve permanent changes to DNA. It can also operate through more flexible mechanisms such as epigenetics. These modifications do not alter the genetic sequence, but rather the way genes are activated or silenced in response to the environment.
Along these lines, researchers from Emory University explored how Andean populations have adapted to another extreme challenge: altitude. Unlike the Tibetans, who have well-identified genetic variants to survive with less oxygen, the Andean peoples do not show such a clear genetic signal. The answer could lie in how your DNA is expressed.
By analyzing epigenetic marks in Kichwa populations from the Ecuadorian Andes and Ashaninka from the Amazon, the scientists found changes in genes related to the vascular system and heart muscle, as well as in the PI3K/AKT pathway, involved in muscle growth and the formation of blood vessels. These modifications could explain physiological characteristics such as arterial thickening or increased blood viscosity, responses to the environment of low oxygen availability.
“The findings are particularly interesting because we are not seeing these strong signals in the genome, but when we look at the methylome these changes do appear,” explains John Lindo, professor of anthropology at Emory and lead author of the study, in a statement from the institution.
The comparison with Tibet reinforces the idea that there is no single way to adapt. On the Tibetan plateau, evolution took another path. A study led by anthropologist Cynthia Beall analyzed hundreds of women who live between 3,000 and 4,000 meters of altitude in Nepal and found that those with greater reproductive success did not have high hemoglobin levels, as one would expect, but rather greater efficiency in oxygen transport.
Part of this advantage comes from a variant of the EPAS1 gene, inherited from the Denisovans, an extinct human species. This adaptation allows maintaining good oxygenation without thickening the blood, avoiding overload of the cardiovascular system.
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“Adaptation to high-altitude hypoxia is fascinating because the stress is severe, it is experienced equally by everyone at a given altitude, and it is quantifiable,” Beall explained. “It is a beautiful example of how and why our species exhibits so much biological variation.”
Together, these findings paint a dynamic picture of human evolution. Far from being a closed process, it is still ongoing. In the Andes, prolonged exposure to natural toxins and a lack of oxygen has shaped genetic, epigenetic and physiological responses. In Tibet, the same problem found different solutions.
