Researchers have long wondered why Tibetans can live at elevations that cause some humans to become life-threateningly ill. A new study answers that mystery, in part, by showing that through thousands of years of natural selection, those hardy inhabitants of south-central Asia evolved 10 unique oxygen-processing genes that help them live in higher climes.

In a study published on Thursday in Science Express, researchers from the University of Utah School of Medicine and Qinghai University Medical School in China report that thousands of years ago, Tibetan highlanders began to genetically adapt to prevent polycythemia (a process in which the body produces too many red blood cells in response to oxygen deprivation), as well as other health abnormalities such as swelling of the lungs and brain (edema) and hypertension of the lung vessels leading to eventual respiratory failure.

Even at elevations of 14,000 feet above sea level or higher, where the atmosphere contains much less oxygen than at sea level, most Tibetans do not overproduce red blood cells and do not develop lung or brain complications. The Utah and Chinese researchers found evidence that this might be related to at least 10 genes, two of which are specific genes strongly associated with hemoglobin, a molecule that transports oxygen in the blood.

High-altitude lung and brain complications threaten and even kill mountaineers who scale the world's tallest peaks. Others who find themselves at elevations significantly higher than where they normally live and work also can be stricken with the condition.

Adaptations to living at higher altitudes have occurred in humans more than once, such as with people indigenous to the Andes Mountains in South America and people native to high altitude regions in the Ethiopian mountains in Africa.

But the Tibetans have evolved genes that others living at similar elevations have not developed, according to Lynn B. Jorde, professor and chair of human genetics at the University of Utah School of Medicine and a senior author on the study.

"For the first time, we have genes that help explain that adaptation," Jorde said.

Although much work remains, and there could be other physiological reasons for the Tibetans' ability to thrive at higher elevations, the researchers believe those 10 genes might have allowed the Tibetans to evolve more efficient metabolisms and not overproduce red blood cells in response to thinner air. The Tibetans also show higher levels of nitric oxide, a molecule that may help get more oxygen to tissues and prevent polycythemia.

"This might help make up for having fewer red blood cells," Jorde said.

A detailed understanding of these changes may eventually lead to targeted therapies for common human maladies, including pulmonary hypertension and lung and brain edema, which affect people everywhere.

(Xinhua News Agency May 14, 2010)