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2013

Mountain Populations Offer Clues to Human Evolution
New York Times, May 2013
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In the hearts of evolutionary biologists, mountains occupy a special place. It’s not just their physical majesty: mountains also have an unmatched power to drive human evolution. Starting tens of thousands of years ago, people moved to high altitudes, and there they experienced natural selection that has reworked their biology.

“This is the most extreme example in humans that you can find,” said Rasmus Nielsen, an evolutionary biologist at the University of California at Berkeley.

Humans have adapted to mountainous environments just as Charles Darwin predicted. To discover how this occurred, scientists are now examining the DNA of people who scaled mountains in different parts of the world.

“There’s this beautiful experiment in natural selection going on,” says Anna Di Rienzo, a professor of human genetics at the University of Chicago. “You can really ask questions central to evolutionary biology.”

When people from low elevations climb to higher ones, they start struggling for oxygen. At 12,000 feet, each breath delivers only 60 percent of the oxygen that the same breath would at sea level. Even a slow walk can be exhausting, because the body can get so little fuel.

In the face of this stress, people respond in several ways. They produce more hemoglobin, the molecule that ferries oxygen from the lungs. Their resting heart rate increases, as does their breath rate. These adjustments help raise the amount of oxygen in the blood, but it never regains its former level.

Extra hemoglobin is not a good long-term solution to life at high altitudes, because it can lead to blood clots. Women moving from low altitudes to high ones also have more trouble delivering oxygen to their babies during pregnancy. Studies have shown that the rate of low-birth-weight babies is twice as high at 6,000 feet as it is at sea level.

Life in the mountains is easier for people whose ancestors have lived there for millenniums. They don’t suffer from altitude sickness. Women from high-altitude populations give birth to normal-size babies.

Scientists visiting some of those populations have discovered a number of biological adaptations in the inhabitants’ bodies. In Tibet, for example, people have broader arteries and capillaries. In the Andes, they can dissolve more oxygen into their blood.

Evolutionary biologists reasoned that natural selection produced these adaptations as each population settled at a high elevation. People with mutations that let them withstand low oxygen levels would be more likely to survive and have healthy children. Several teams of scientists have traveled to the mountains to gather DNA samples from people and search for traces of that evolution.

In 2010, Dr. Nielsen and his colleagues found variants of certain genes that were much more common in Tibetans than in the Han, the major ethnic group in China, who have lived for thousands of years at lower altitudes. By a wide margin, the winner was a gene called EPAS1. People with different variants turned out to have different levels of hemoglobin, suggesting that the gene was important to adapting to life at high altitudes.

Recently, Dr. Nielsen and another group of colleagues published a study on people who live in the highlands of Ethiopia. They found no evidence that EPAS1 had evolved there as it did in Tibet. Instead, a different gene, BHLHE41, appeared to have experienced natural selection.

Two other teams of scientists have recently searched for high-altitude genes in Ethiopians, and neither put BHLHE41 on their list. It’s possible that Dr. Nielsen’s method is more sensitive than the others, but that remains to be proved. “It’s going to take a while to sort through the discrepancies in Ethiopia,” said Dr. Di Rienzo, a co-author of one of the other studies.

It will be intriguing to see that unfold. BHLHE41 and EPAS1 turn out to have something in common: they work together in a network of genes that lets us cope with low oxygen levels. Even at sea level, low oxygen can threaten our bodies from time to time. Exercise can strip it from our muscles, while inflammation can eliminate it from wounds. The oxygen-sensing pathway triggers defenses to protect our bodies from damage.

Dr. Nielsen’s study suggests that evolution has stumbled across a way to retool this pathway to help people live at high altitudes. But it turns out there’s more than one way to retool a pathway. Though evolution has some creative freedom, it seems to stick to a few themes.

Copyright 2013 The New York Times Company. Reproduced with permission.
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