Researchers at Emory University have published new findings on how Indigenous populations in the Andes may have adapted to high-altitude environments through epigenetic changes, rather than genetic mutations commonly seen in other highland groups.
The study, published in Environmental Epigenetics, was led by Yemko Pryor as part of her doctoral work at Emory. The research team analyzed the methylomes—chemical modifications that affect gene expression—of 39 individuals from two Indigenous groups: the Kichwa from Ecuador’s Andean highlands and the Ashaninka from the Amazon Basin lowlands. This approach differs from previous studies that searched for specific genetic variants linked to altitude adaptation.
“This is the first whole methylome data on these two populations,” said Pryor. “Unlike many methylome studies that focus on just a few hundred thousand sites throughout the genome, we looked at all three million base pairs to see what we would find.”
The analysis revealed significant differences in DNA methylation between the two groups. Notably, changes were observed in genes associated with vascular regulation (PSMA8) and heart muscle function (FST). Genes within the P13K/AKT pathway, which are related to muscle growth and blood vessel formation, also showed strong signals among high-altitude dwellers.
Researchers suggest these epigenetic patterns may explain physiological adaptations seen in Andean populations, such as increased muscularization of small arteries and higher blood viscosity. These adaptations appear distinct from those found among Tibetans living at similar altitudes. The P13K/AKT pathway has been previously linked to arteriole wall thickening under low-oxygen conditions in both animal models and human cells. The authors note that pulmonary hypertension is more common among Andean highlanders than other mountain populations.
Additionally, the study found marked differences between the two groups in methylation of 39 pigmentation-related genes, which could be linked to adaptation against strong ultraviolet radiation experienced at high elevations.
“The findings are particularly interesting because we’re not seeing these strong signals in the genome but when we look at the methylome, we are seeing these changes,” said John Lindo, associate professor of anthropology at Emory and senior author of the study.
Lindo explained that while gene selection theory focuses on inherited genetic traits for adaptation, epigenetic changes represent flexible responses to environmental factors that might not be passed down directly to offspring. He noted: “The Kichwa population that participated in our study did not just arrive in the Andean highlands — their ancestors had been living there for nearly 10,000 years. Our findings suggest that epigenetics can contribute to adaptation in a longstanding way.”
The research involved collaboration with scientists from institutions including Central University of Ecuador; Institute of Medicine and Forensic Sciences in Lima, Peru; State University of Rio de Janeiro; and University of Pavia in Italy.
Lindo established Emory’s Ancient DNA Laboratory in 2020 to investigate how environmental changes have influenced human biology across time periods. The lab collaborates closely with Indigenous communities and local researchers during its projects.
Pryor highlighted her experiences working both inside and outside the laboratory: “As a scientist doing research on humans, it’s also important to go beyond the data and be in community with people,” she said. “As much as I love doing analyses in the lab, it was a beautiful experience for me to get to go into the field and engage directly with people there.”
To share their results directly with participating communities, co-author Daniel Rivas Alava is developing workshops tailored for Kichwa participants.
Pryor has since completed her PhD at Emory and is now conducting postdoctoral research at the University of Michigan focused on human pigmentation genetics. She credits her time at Emory for providing key analytical skills: “I’m applying many of the techniques I learned at Emory, especially computational skills,” she said. “My dream is to stay in academia and start my own ancient DNA lab one day.”
