Researchers at Emory University have used DNA methylation analysis to investigate how Indigenous populations in the Andes have adapted to life at high altitudes. While previous studies identified a specific gene variant in Tibetans that increases oxygen-carrying capacity, similar genetic signals were not found among Andean highlanders.
The study, published in Environmental Epigenetics, compared the methylomes—markers of epigenetic changes—of 39 individuals from two groups: the Kichwa from Ecuador’s Andean highlands and the Ashaninka from the lowland Amazon Basin. This is the first time whole methylome data has been generated for these populations.
“This is the first whole methylome data on these two populations,” said Yemko Pryor, first author and former Emory PhD student. “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 researchers found notable differences in DNA methylation related to genes involved in vascular regulation (PSMA8) and heart muscle function (FST). They also observed strong signals for genes within the P13K/AKT pathway, which is associated with muscle growth and new blood vessel formation. These epigenetic patterns may explain previously observed traits in Andean highlanders such as increased muscularization of small arteries and higher blood viscosity.
The study suggests that these adaptations are different from those seen in Tibetan populations and may represent a unique response to low-oxygen environments. The P13K/AKT pathway has been linked to arteriole wall thickening under hypoxic conditions in both rats and human cells. Arteriole wall thickening is associated with pulmonary hypertension, which occurs more frequently among Andean highlanders than other high-altitude groups.
Additionally, significant differences were identified between the two groups in the methylation of 39 pigmentation-related genes, possibly reflecting adaptation to stronger ultraviolet radiation at higher 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.
Gene selection theory suggests adaptive genetic traits should be inherited and detectable within DNA sequences. However, epigenetic changes offer more flexible responses to environmental pressures and may not always be passed down through generations.
“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,” Lindo said. “Our findings suggest that epigenetics can contribute to adaptation in a longstanding way.”
The research team included scientists from Central University of Ecuador; Institute of Medicine and Forensic Sciences in Lima, Peru; State University of Rio de Janeiro; and University of Pavia, Italy.
Lindo established Emory’s Ancient DNA Laboratory in 2020. The lab works closely with Indigenous communities and local scientists on collaborative projects, ensuring participants have access to research findings. As part of this commitment, workshops will be held for Kichwa and Ashaninka communities to share results directly.
“I was one of the first graduate students to join the lab,” said Pryor. “I learned how to build a lab from the ground up while also getting hands-on analytical and technical skills.” She now continues her research as a postdoctoral fellow at the University of Michigan.
“As a scientist doing research on humans, it’s also important to go beyond the data and be in community with people,” Pryor added. “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.”
A co-author on this paper is Daniel Rivas Alava, an Emory graduate student who is developing educational workshops for participating communities.
“My dream is to stay in academia and start my own ancient DNA lab one day,” Pryor said.
