New research used whole-methylome sequencing to study how Indigenous people adapted to the Andean highlands, an environment with low oxygen, cold temperatures and strong ultraviolet radiation. Rather than scanning the genome for inherited DNA variants, the team examined DNA methylation across the methylome, a type of epigenetic modification that alters gene expression in response to the environment. The study appears in the journal Environmental Epigenetics.
The researchers analyzed samples from 39 individuals in two modern Indigenous populations: the Kichwa from Ecuador's Andean highlands and the Ashaninka from the lowland Amazon Basin along the Peruvian border. This is the first whole-methylome dataset for these groups, and the assay covered all available sites rather than the few hundred thousand often tested in other studies.
They found strong methylation differences between the high- and low-altitude groups. Key signals involved PSMA8, a gene tied to vascular regulation; FST, linked to heart muscle regulation; and genes in the P13K/AKT pathway, which is associated with muscle growth and formation of new blood vessels. The authors suggest these epigenetic patterns may help explain traits in Andean highlanders — for example, increased muscularization of small arteries and higher blood viscosity — and note that arteriole wall thickening under low oxygen has been linked to pulmonary hypertension in animal and cell studies.
- Epigenetic changes can be more flexible than inherited DNA changes.
- The Kichwa ancestors had lived in the highlands for nearly 10,000 years.
- Coauthors include scientists from universities in Ecuador, Peru, Brazil and Italy.
Difficult words
- methylome — complete set of methylation sites in DNAwhole-methylome, the methylome
- methylation — chemical addition to DNA that affects gene activityDNA methylation
- epigenetic modification — environment-linked change that alters gene activity
- gene expression — process by which genes make their products
- vascular regulation — control of blood vessel behavior and blood flow
- muscularization — increase in muscle tissue or muscle development
- blood viscosity — thickness or resistance of blood to flowing
- pulmonary hypertension — high blood pressure in the lungs' blood vessels
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Discussion questions
- How might flexible epigenetic changes offer advantages over inherited DNA changes for people living at high altitude? Give reasons from the article.
- The article links arteriole wall thickening to pulmonary hypertension in studies. What might be the possible benefits and risks of thicker arteriole walls for highlanders?
- Why is it important that this study used a whole-methylome assay covering all available sites rather than testing only a few hundred thousand sites?
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