Researchers Identify Genetic Adaptation for High Altitudes

Researchers have identified the genetic framework under which people can adapt to living in low-oxygen, high altitude settings.

By pinpointing the genetic basis of adaptation to high altitudes, researchers hope to be able to develop more effective treatments for Monge's disease, also known as chronic mountain sickness (CMS).

Low-oxygen, high altitude conditions present numerous physical challenges to the more than 140 million people who live in such conditions around the world.

Some populations of high altitude-dwelling people have adapted to cope with hypoxia, or low levels of oxygen in the blood. Yet others, particularly people living in the Andes mountain region of South America, are maladapted and suffer from CMS.

CMS is characterized by an array of neurological symptoms such has headache, fatigue, sleepiness, depression. Often people with CMS will suffer strokes or heart attacks early in life. CMS is commonly found in people living in the Andes and occasionally in Tibetans, but the condition is notably absent in Ethiopians living in in high-altitude regions of East Africa.

Researchers sought to pinpoint the genetic mechanisms underlying high-altitude adaptation by comparing the genomes of Andean people with CMS and those of others living in high altitudes without CMS.

After analyzing the complete genomes, the researchers pinpointed two genes -- ANP32D and SENP1 --  which, the researchers wrote, "significantly increased expression in the CMS individuals when compared to the non-CMS individuals," suggesting that "down-regulating these genes could be beneficial in coping with hypoxia."

"While a number of published articles have described an association between certain genes and the ability for humans to withstand low oxygen at high levels, it was very hard to be sure if the association was causal," said principal investigator Gabriel G. Haddad of the University of California San Diego School of Medicine.

Haddad and his colleagues then looked at the genomic sequence of fruit flies subjected to the conditions of hypoxia.

"We found that flies with these genes down-regulated had a remarkably enhanced survival rate under hypoxia," said Haddad.

"Their findings have important implications -- not only for those who live at high altitudes, but also in treating certain cardiovascular and brain diseases related to low oxygen levels in individuals living at any altitude," the university wrote in a statement.

Haddad and his colleagues' work was published online in advance of its upcoming publication in the American Journal of Human Genetics.