How Ethiopian Highlanders Adapted To Their Low Oxygen Conditions

Patchwork of farms in the Ethiopian highlands. John Wollwerth/Shutterstock.
Janet Fang 06 Aug 2015, 01:06

The Ethiopian highlands are about 3,500 meters above sea level, yet a case of chronic mountain sickness has never been reported among native highlanders. Now, researchers may have uncovered the genetic adaptation that helped Ethiopians to adjust to life in low oxygen conditions over evolutionary time. The findings were published in Proceedings of the National Academy of Sciences this week. 

People have been living in high-altitude locales for thousands of years. There are more than 140 million people living 2,500 meters above sea level or higher. Previous work suggests that three high-dwelling populations – Andeans, Himalayans, and Ethiopians – have adapted unique ways to cope with these extreme environments. In a 2014 study, researchers trying to understand the basis for high-altitude adaptations analyzed the whole genomes of 13 native Ethiopian highlanders for genetic variation. Six of the participants live on the Bale Plateau, and the other seven individuals live on Chennek field in the Simien Mountains. This work highlighted certain genes linked to adaptations for hypoxia, a condition caused by oxygen deficiency.

Now, a UC San Diego team led by Gabriel Haddad tested one of those genes called endothelin receptor B (EdnrB). Its product is a signaling receptor involved in cardiac function. They exposed genetically engineered mice – who have only one functional copy of the gene – to moderate or extreme hypoxia (just 5% oxygen). Compared to control mice, these mutant mice showed better cardiac performance and oxygenation of vital organs. Decreased EdnrB, it seems, improves cardiac tolerance to hypoxia. 

When they conducted a gene expression analysis, the team identified several genes that might help to explain this superior cardiac function under severe hypoxia. Three of these genes – Nppa, Sln and Myl4 – were implicated in cellular pathways involved in calcium regulation, heart contraction, and blood circulation. 

If lowering levels of EdnrB helps to preserve cardiac function in hypoxic conditions at high altitudes, understanding this better could help people to maintain optimal oxygen balance at various other altitudes.

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