In the Andes, High Altitude Stealthily Alters Genes for Adaptation to Life Among the Clouds

Between the short breath of the summits and the atmospheric pressure which crushes gas exchanges, the air from high altitudes profoundly transforms the functioning of the human body. Some peoples not only survive there, they have flourished there for nearly 10,000 years. However, contrary to what one might believe, this ability is not necessarily written in the genes. Another form of adaptation, more flexible and reversible, seems to play a key role in this biological performance.

Systemic effects of thin air on the human body

Above 2,500 meters, the partial pressure of oxygen drops significantly, reducing blood and tissue oxygenation. This chronic hypoxia disrupts energy production, cellular function and growth. However, bodies acclimated over generations have put in place effective countermeasures.

Tibetan populations show a particularly strong ventilatory response, while Andeans show higher hemoglobin levels, more lung growth, and altered blood flow distribution. A study published in the Journal of Applied Physiology highlights that these differences are not solely the result of the environment, but reflect progressive natural selection which has optimized the distribution of oxygen in tissues.

This response manifests itself from childhood. Among the Andeans, the lungs grow faster, the heart adapts to the pressure and circulation is directed to the essential organs. This profound remodeling does not only affect physiology. It extends to the regulation of the genes themselves, via an even more discreet mechanism.

Adaptation to high altitude modifies gene networks without altering DNA

Instead of relying solely on inherited mutations, some populations modify their genetic activity without changing their DNA sequence. This process is called epigenetics. In Kichwa communities living in the Ecuadorian Andes, researchers have discovered molecular adjustments directly linked to living at high altitudes. These are changes in DNA methylation, a mechanism that acts as a cursor on the intensity of gene activation.

The study published in Environmental Epigenetics made it possible to compare the complete methylation profiles of two indigenous groups: the Kichwa at altitude and the Ashaninka in the Peruvian Amazon. As a result, 779 regions of the genome present distinct epigenetic signatures. Two major genes, associated with the response to hypoxia, are less methylated in the Kichwa, which suggests an increased activation of mechanisms linked to the management of lack of oxygen.

Even more surprising, researchers observed more marked methylation of the follistatin gene, involved in muscular and cardiovascular health, in Andean populations. They associate this feature with the increased thickness of arterial walls and higher blood viscosity, two characteristics already documented in previous studies.

According to one of them published in Nature, this type of epigenetic signature reflects a durable but not permanent cellular memory. Researchers observe that methylation profiles are extremely stable at the cellular level and constitute faithful markers of the identity and history of each lineage. But they are not necessarily transmitted to subsequent generations, unlike genetic mutations.

An adaptive strategy specific to Andean populations

The Andeans are distinguished by the balance they build between plasticity and stability. While natural selection has fixed certain specific mutations in the Tibetans, such as that of the EPAS1 gene, Andean populations regulate their genes dynamically to adapt to altitude. This gives them a more flexible ability to adjust to changing environmental conditions. ScienceAlert insists on the fact that these modifications can be lasting but not definitive, which suggests a form of modular adaptive heritability, without guarantee of transmission.

For the moment, studies have not decided on the capacity of these epigenetic marks to cross the generation barrier. As highlighted in the journal Frontiers in Epigenetics and Epigenomics, intergenerational transmission of the epigenome in mammals remains a controversial subject. Biological cleaning mechanisms exist precisely to prevent subsequent generations from inheriting all the “environmental baggage” accumulated by their ancestors.

Epigenetics therefore appears to be a subtle interface between the environment and the expression of our genome. Far from being an alternative to evolution, it constitutes a complementary ramification. Faster, more flexible, but also more fragile. Among the Andeans, this flexibility seems to have been established over time, offering a rare model of adaptation without mutation.