High elevations within the Ecuadorian Andes, situated thousands of meters above sea level, present human inhabitants with environmental challenges distinct from those encountered at lower elevations.
The human organism possesses the capacity for physiological acclimatization to the reduced oxygen availability characteristic of rarefied atmospheres. Moreover, elevated levels of ultraviolet radiation pose a significant environmental hurdle in high mountain ecosystems.
Over extensive periods, these ecological pressures can influence the perpetuation of specific genetic endowments across successive generations. Indigenous populations, for instance, exhibit pronounced physiological distinctions compared to individuals who have recently relocated to these altitudes, as evidenced by scholarly research demonstrating enduring variations.
Furthermore, the body’s physiological response to altitudinal variations can impact gene expression patterns. This phenomenon has recently been documented within Indigenous Andean Kichwa communities. While this does not represent genetic evolution in the classical sense, it underscores the adaptive, epigenetic mechanisms that cellular systems employ to adjust to their surroundings by modulating the activity of existing genetic material.
The question of whether these epigenetic modifications are passed down through generations in humans remains an open area of investigation. Definitive evidence regarding the persistence of these alterations across lineages is currently lacking, as the scope of the investigation was limited to contemporary populations and did not encompass longitudinal changes over time.
The planet hosts a remarkable diversity of environments, and human groups residing in specific ecological niches can develop specialized adaptations tailored to those conditions. Consider, for example, free divers in South Korea, who possess inherent genetic advantages that enhance their capacity for oxygen storage and release during prolonged underwater excursions.
What particularly captured the attention of a research cohort spearheaded by anthropologists Yemko Pryor and John Lindo at Emory University in the United States was the divergence in adaptation strategies. While individuals inhabiting the Tibetan Plateau exhibit robust indicators of evolutionary genetic shifts associated with high altitude, which have been inherited over generations, populations residing in the Andes at comparable elevations display different adaptive changes that may not be genetically heritable. This disparity raises pertinent questions regarding their acclimatization to altitudes exceeding 2,500 meters (8,200 feet).
Instead of undertaking a comprehensive re-examination of the entire Andean genome, the researchers adopted an alternative methodology: the analysis of the methylome.
Imagine DNA as a comprehensive biological manual containing all instructions for bodily functions. The methylome, in this analogy, can be likened to a set of adjustable bookmarks that can modulate the activity of specific genes without altering the underlying DNA sequence. These are transient modifications superimposed on the DNA structure, typically resulting in a directive to ‘reduce the activity of this particular function’.
Researchers collected biological samples from 39 individuals belonging to Indigenous communities dwelling at high altitudes in the Ecuadorian Andes and in the Peruvian Amazon Basin: the Kichwa and Ashaninka groups, respectively. Subsequently, the complete methylome was sequenced from each participant, enabling a comparative analysis between the two cohorts.
“This represents the inaugural comprehensive methylome dataset for these two populations,” stated Pryor. “Unlike numerous prior methylome studies focusing on a limited subset of genomic sites, our investigation encompassed all three [billion] base pairs to ascertain the full spectrum of findings.”
The comparative analysis revealed 779 distinct differences between the high-altitude and low-altitude populations, encompassing specific modifications pertinent to the environmental conditions of high-altitude living.
These findings do not indicate heritable genetic alterations but rather suggest short-term physiological adaptations developed in response to living at elevated altitudes.
Notably, two genes implicated in the body’s response to hypoxia (oxygen deficiency) exhibited differential methylation. Reduced methylation levels for both genes were observed in the Kichwa communities residing at high altitudes.
This observation points to a regulatory adjustment in how these genes might respond to diminished oxygen availability, aligning with prolonged exposure to thin air, though it does not provide direct evidence of a blunted emergency response mechanism.
Concurrently, the follistatin gene, integral to cardiovascular and muscular function, as well as the body’s resilience to oxygen stress, was found to be hypermethylated. This finding suggests a potential correlation with established physiological characteristics of Andean populations, such as increased arterial wall musculature and elevated blood viscosity.
The researchers posited that this might be connected to alterations identified within the PI3K/AKT signaling pathway, which plays a pivotal role in various cellular processes, including metabolism and cellular survival.
Finally, a cohort of 39 genes associated with skin pigmentation demonstrated statistically significant variations between lowland and highland inhabitants, consistent with exposure to differing levels of ultraviolet radiation at higher elevations.
Collectively, these outcomes imply that heritable genetic changes may represent only one facet of our adaptive repertoire, and that epigenetic modifications influencing gene activity within an individual’s lifetime could indeed contribute significantly.
“The Kichwa individuals who participated in our research were not recent arrivals to the Andean highlands; their ancestors had been established there for approximately 10,000 years,” remarked Lindo. “Our findings lend support to the notion that epigenetic mechanisms can facilitate long-standing adaptation.”
