October 2010, update August 2014, update August 2022

If you live in the lowlands, you may have experienced the huffing and puffing that typically accompany a trip to higher altitudes. That’s because oxygen levels go down as one goes up. Travelling to Denver from sea level means a 17% decrease in available oxygen. Our bodies compensate for even this small change with faster breathing and a higher heart rate — at least until we acclimate to the thinner atmosphere. And a loftier vacation spot (for example, La Paz, Bolivia at 11,942 feet) could bring on serious altitude sickness with insomnia, nausea, and swelling — but not for everyone. Tibetan highlanders have no trouble living at 13,000 feet year in year out, and many Nepalese Sherpas (who are ethnically Tibetan) climb parts of Mount Everest without the supplementary oxygen most people require. How do they do it? New research makes it clear that Tibetan highlanders haven’t just acclimated to their mountain home; they’ve evolved unique physiological mechanisms for dealing with low oxygen levels.

Where's the evolution?

The evolutionary adaptations that allow Tibetans to function at high altitudes are very different from the acclimatization process that most of us go through when we spend time in those places. When lowlanders visit Denver, La Paz, or Lhasa, for example, their bodies begin to produce more red blood cells — the purveyors of oxygen in the body. These extra cells seem to help transport available oxygen around the body — and may eventually compensate for decreased oxygen levels, allowing breathing and heart rate to return to normal. This is an example of phenotypic plasticity, shifts in an organism’s body, physiology, or behavior that are dependent upon the environment it occupies, not upon a genetic change. The switch to producing more red blood cells that occurs when a lowlander visits Lhasa does not reflect a new mutation, but rather the body’s response to a new environment. Because they don’t reflect a shift in the genetic makeup of a population, such changes, which occur within the lifespan of a single individual, are not adaptations in an evolutionary sense.

The Tibetan highlander population, on the other hand, has, over the course of thousands of years, evolved adaptations that allow individuals to thrive in a low oxygen environment. Paradoxically, one of these adaptations is almost exactly the opposite of a lowlander’s response to high altitude: Tibetans have gene versions that cause them to produce fewer red blood cells. How is that helpful? It turns out that extra red blood cells make blood thicker — more like honey than water — and after a certain point, this cell-laden blood can actually get so thick that it doesn’t pass through capillaries efficiently to oxygenate cells. Having blood with too many red blood cells can be particularly problematic during pregnancy since it is linked to slow fetal growth and high rates of fetal mortality. One study found that Han Chinese people (lowland relatives of Tibetans whose bodies respond to high altitudes by producing more red blood cells) living in the Tibetan highlands were three times as likely to suffer pre- or post-natal infant death than were ethnic Tibetans! In the long run, producing extra red blood cells may do more harm than good.

The basis for the Tibetans’ adaptation is not a change in a gene that produces hemoglobin or any one of the other proteins that make up red blood cells. Instead, the key change seems to be in a stretch of DNA (called EPAS1), which codes for a regulatory protein. This protein senses oxygen and helps control the process of producing red blood cells. The change in EPAS1 seems to make Tibetans less likely to overproduce red blood cells at extreme altitudes and, hence, probably helps them to avoid altitude sickness and deliver oxygen more effectively to developing fetuses. Other unique traits of Tibetans (a higher breathing rate and blood vessels which expand to allow better oxygen transport) likely also contribute to their altitude aptitude.

Scientists recently narrowed in on this explanation through a series of studies that all pointed to EPAS1 as a key player in Tibetans’ altitude adaptation. One group of biologists compared the genomes of ethnic Tibetans to the genomes of Han Chinese individuals, as well as to the genomes of distantly related Danes. The basic reasoning was that if a particular gene version is found at high frequency in Tibetans and low frequency in their close and distant relatives, that gene version probably rose to high frequency in the Tibetan population recently through the action of natural selection. The most extreme differences in gene version frequency the scientists observed were in the EPAS1 gene. Another group of scientists observed similar gene frequency differences between Tibetans and Han Chinese in and around the EPAS1 gene. This group of researchers also found that the genetic variants of EPAS1 that were most common in Tibetans were linked to lower levels of hemoglobin, which indicates lower red blood cell counts. All of those observations made a lot of sense in light of what was already known about the function of EPAS1 and fit with previous observations of Tibetans’ low red blood cell counts at high altitudes, their resistance to altitude sickness, and their relatively high fertility at high altitudes. All the different lines of evidence point to the same explanation: the EPAS1 gene and the region around it seems to have been a target of selection as Tibetans moved to higher altitudes and faced the challenges of a low-oxygen environment.

Some genetic studies estimate that the Tibetans split from the Han Chinese population and began migrating to the highlands less than 3000 years ago — and that all this adaptation to living tens of thousands of feet above sea level has occurred in just a hundred or so generations. If that estimate is accurate, this would represent the fastest example of human evolution yet documented.

Although Tibetans’ altitude adaptation may be unusually rapid, it is not unique. As humans moved out of Africa and diverged into populations that reside in very different environments — from the heights of the Andes to the bitter cold of Siberia to the tiny islands of the Pacific — these groups experienced natural selection which favored traits well-suited to their conditions and weeded out others. Scientists have studied adaptations that allow Europeans and many Africans to digest lactose, that help Eskimos keep warm, and that allow Europeans to synthesize vitamin D. So the next time you are huffing and puffing up a mountain (or not), drinking a glass of milk (or not), or bundling up in a parka (or not), take a moment to reflect on the unique evolutionary history that has shaped who you are today.