The Altitude Gene, A Denisovan Gift

Jan. 23, 2015

By Medical Discovery News

Altitude Gene, A Denisovan Gift

Those traveling to the Himalayas have a tough time adjusting to the harsh altitude. But for those native to Tibet, called the Roof of the World due its location 14,700 feet up, it’s not a problem. That’s because Tibetans have adapted to this harsh environment partly due to a gene they inherited from an extinct species of prehumans called the Denisovans.

Anyone traveling to high altitudes like those in Tibet can get altitude sickness and there is no way to predict who will get it. The severity of it varies according to genetics and the rate of ascent, but it is not influenced by age, gender, physical fitness, or previous altitude experience. Symptoms can include headaches, nausea, dizziness, fatigue, shortness of breath, loss of appetite, and disturbed sleep. Severe symptoms could indicate high altitude cerebral edema, which impairs brain function, progresses rapidly, and can become life-threatening in a matter of hours.

However, Tibetans live at these extreme altitudes without developing these problems. So how did they adapt to such a challenging environment?

Studies have linked the Tibetan’s adaptation to high altitude with several genes, including a unique form of the EXPAS1 gene. This gene responds to low oxygen levels to increase hemoglobin production. However, Tibetans with this gene do not have elevated levels of hemoglobin. This seems counterintuitive, since increasing hemoglobin could increase the amount of oxygen being transported in the blood. This would be advantageous at altitudes where the availability of oxygen is reduced, which then limits the uptake of oxygen in the lungs. On the other hand, increasing red blood cells would also thicken the blood, making it less efficient in distributing oxygen and increasing the risk of stroke. The Tibetan variant of EXPAS1 gene might then be protective, but we don’t know how exactly it works.

We know that the ancestors of Nepal’s Sherpa people carried the Tibetan EXPAS1 gene variant about 30,000 years ago. Today, only Tibetans carry this version of the gene, no other modern humans have it. New data suggests it may have come from an extinct population of prehuman called the Denisovans. So far they have only been found in a cave in the Altai Mountains in southern Siberia in East Central Asia. More proof is needed to eliminate another extinct species, the Neanderthals, who also have a version of EXPAS1 similar to the Tibetan one. This is another example of genes acquired by interbreeding between Homo sapiens and other ancient species. About 5 percent of the genetic information of Australasians is shared with Denisovans, while 2.5 percent of human DNA originates from Neanderthals. Modern humans have bits of DNA from these ancient species that have made important contributions to the success of our genome.

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High Altitude Sickness

June 21, 2013

By Medical Discovery News

For those visiting Denver or other mile-high cities, the incredible panoramic views may be overshadowed by headaches that worsen with higher altitudes. Such headaches are a common symptom of altitude sickness, but it is impossible to predict who will react to high altitudes and the severity of those symptoms. And now, research shows that serious altitude sickness may result in long-term brain damage.

Contrary to popular belief, the concentration of oxygen at higher altitudes is the same as sea level, about 21 percent. But the atmospheric pressure changes significantly, from 760 millimeters of mercury at sea level to only 410 millimeters of mercury at the top of Longs Peak in the Rocky Mountains. That 46 percent drop in pressure allows oxygen molecules to be spaced farther apart in the air. As a result, a person breathes in fewer oxygen molecules in each breath.

To compensate, the body breathes faster to take in more oxygen molecules and maintain blood oxygen levels. But this adjustment generally takes one to three days, which explains why the No. 1 cause of altitude sickness is going too high too fast. Then the body can’t keep healthy oxygen levels and the amount of oxygen in the body lowers, called hypoxia. This can cause fluid to leak from small blood vessels called capillaries and accumulate in the lungs and the brain. While some cases of altitude sickness end with headaches, the added stress on the lungs, heart, and arteries can lead to serious consequences, including death.

When fluid continues to leak into the brain, an incredibly dangerous condition known as high altitude cerebral edema (HACE) can develop. Symptoms include inhibited mental function, hallucinations, loss of coordination, impaired speech, personality changes, nausea, and coma. The only treatment options are to move the person to lower altitude (10,000 feet or less) or put them in a high-oxygen hyperbaric chamber. Doctors used to believe that once treated, patients fully recovered.

However, a new study looked at brain scans of 36 mountain climbers and found several small blood vessels leaking into brain tissue in eight of the 10 climbers with earlier cases of HACE. Only two of the other 26 climbers without previous case of HACE had similar leaks, called microhemorrhages. This shows that a person’s chance of developing mircohemorrages probably increases with HACE. The severity of the hemorrhages correlated to the severity of the climber’s HACE. It’s unclear if more time in high altitudes affects the lesions or what their long-term consequences may be.

Earlier studies showed that almost every MRI of a Mt. Everest climber showed evidence of brain damage. Even amateur climbers, climbers of lesser altitudes, and climbers with no symptoms of altitude sickness showed some sign of brain damage. The damage was still evident years later, even if the climber no longer went to high altitudes.

This recent finding has raised many questions; for example, do HACE victims have an increased incidence of developing dementia or other neurological disorders?  More studies are necessary to verify the results of long-term changes to the brain as a result of high altitudes and HACE. Mountain climbers need to be aware of these risks before they pursue that next peak.

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