Mutations in same gene allow two different groups of humans to thrive at extreme altitudes.
The high life is a lot harder than it sounds. Most people are accustomed to living at low elevations and struggle to breathe at high altitudes. But thin air isn’t a problem for the Quechua people of Peru, who have survived—and thrived—high in the Andes Mountains for more than 10,000 years.
A new study has pinpointed a genetic variant that may have helped this population adapt to life at extraordinary heights. Tibetans in the Himalayas possess a different mutation in the same gene, suggesting both groups independently evolved similar adaptations to high-altitude living. The finding demonstrates “how evolution can sometimes favor common solutions to a common problem,” says Graham Scott, a physiologist at McMaster University who wasn’t involved in the study.
The human body is best suited for life at or just above sea level, where oxygen is plentiful. Venture above 2500 meters, and you may suffer the effects of altitude sickness—a type of hypoxia that can cause nausea, confusion, and swelling of the lungs and brain. Living at high altitudes for long periods can cause chronic mountain sickness, boosting the risk of heart problems, stroke, and complications during pregnancy and birth. But certain populations, including South American and Tibetan highlanders, can live and work comfortably at altitudes of more than 4000 meters.
Although these groups share some physiological traits—larger lungs, for example—some of the underlying mechanisms that help them cope with highland living are quite different. A 2014 study found that Tibetans have evolved adaptations to increase body weight and boost the production of nutrients, whereas a 2018 paper identified variations in genes related to heart muscle development in Andean populations. Other research suggests growing up in the harsh Andean environment causes epigenetic changes, which don’t alter the actual sequence of DNA but can affect how it’s expressed.
Another important difference between the two groups is that some Andeans appear to have unusually high levels of hemoglobin in their blood, giving them a much-needed oxygen boost, whereas Tibetans get by with below average concentrations.
In 2010, a team that included geneticist Tatum Simonson of the University of California (UC), San Diego discovered that Tibetan highlanders possess several gene variants that let them use hemoglobin more efficiently, thus boosting oxygen in their blood. One is a unique version of a gene called EPAS1, which encodes a transcription factor that “turns on hundreds if not thousands of genes in response to low oxygen,” Simonson says.
has revealed that some Andeans, rather than having higher hemoglobin levels, have yet another version of EPAS1—one that, similar to the Tibetan variant, is associated with low hemoglobin and higher oxygen saturation.
“I was surprised to see that EPAS1 was involved,” says Emilia Huerta-Sanchez, a population geneticist at Brown University who wasn’t involved in the new study. In 2014, Huerta-Sanchez and a team of other scientists found that Tibetan highlanders inherited their unique EPAS1 variant from an ancient human subspecies known as Denisovans, who went extinct some 40,000 years ago. The mutation present in modern Quechua people likely arose about 20,000 years later—around the same time that humans first began living in the Andes.
“Whenever we find instances of convergent evolution, especially within a species in two different populations, it’s exciting,” says Tony Capra, a genomics researcher at UC San Francisco who wasn’t involved in the study. Scientists now have “multiple vantage points” to study how natural selection acts on certain high-altitude adaptations, he says.
Simonson notes that the mutations present in Tibetan populations occur in noncoding regions of EPAS1 and have subtle regulatory effects on the expression of the gene in some tissues. The newly discovered variant, however, is “hard coded in the DNA” and could directly impact the structure or function—or both—of the transcription factor in every single cell. That’s “a huge deal,” she explains.
The team also checked large genome databases for signs of the Andean variant. They found it in a few other human populations, but at extremely low frequencies. “The variant is really, really rare and is pretty much nonexistent in the rest of the world,” says study co-author Wanjun Gu, who worked on the project as a member of Simonson’s lab at UC San Diego.
Bizarrely, the only other organism that shares the variant in high frequencies is the West Indian Ocean coelacanth (Latimeria chalumnae)—a rare species of lobe-finned fish that has persisted for hundreds of millions of years. It’s possible that coelacanths may also have evolved the variant as some species adapted to low-oxygen conditions.
PS; When we first landed in Cusco - Peru, which is at an elevation of 3400m which has only about 13% Oxygen in the air we had problems. There were 7 in the group, three couples and my teenaged son. All took the tablets to acclimatize with high altitude with the exception of myself and my son.
All the males were fine but all the females were affected. One of the ladies just climbed one flight of stairs in the hotel, sat down on the landing, my son helped her to the room and she only came out after nearly three hours later for dinner.
While at dinner in the hotel restaurant one NZ lady collapsed at the next table. We helped her out, the hotel handed the oxygen cylinders immediately as they expect these problems. Also the hotel provides Coca Tea 24 hrs which helps you out for altitude sickness.
The high life is a lot harder than it sounds. Most people are accustomed to living at low elevations and struggle to breathe at high altitudes. But thin air isn’t a problem for the Quechua people of Peru, who have survived—and thrived—high in the Andes Mountains for more than 10,000 years.
A new study has pinpointed a genetic variant that may have helped this population adapt to life at extraordinary heights. Tibetans in the Himalayas possess a different mutation in the same gene, suggesting both groups independently evolved similar adaptations to high-altitude living. The finding demonstrates “how evolution can sometimes favor common solutions to a common problem,” says Graham Scott, a physiologist at McMaster University who wasn’t involved in the study.
The human body is best suited for life at or just above sea level, where oxygen is plentiful. Venture above 2500 meters, and you may suffer the effects of altitude sickness—a type of hypoxia that can cause nausea, confusion, and swelling of the lungs and brain. Living at high altitudes for long periods can cause chronic mountain sickness, boosting the risk of heart problems, stroke, and complications during pregnancy and birth. But certain populations, including South American and Tibetan highlanders, can live and work comfortably at altitudes of more than 4000 meters.
Although these groups share some physiological traits—larger lungs, for example—some of the underlying mechanisms that help them cope with highland living are quite different. A 2014 study found that Tibetans have evolved adaptations to increase body weight and boost the production of nutrients, whereas a 2018 paper identified variations in genes related to heart muscle development in Andean populations. Other research suggests growing up in the harsh Andean environment causes epigenetic changes, which don’t alter the actual sequence of DNA but can affect how it’s expressed.
Another important difference between the two groups is that some Andeans appear to have unusually high levels of hemoglobin in their blood, giving them a much-needed oxygen boost, whereas Tibetans get by with below average concentrations.
In 2010, a team that included geneticist Tatum Simonson of the University of California (UC), San Diego discovered that Tibetan highlanders possess several gene variants that let them use hemoglobin more efficiently, thus boosting oxygen in their blood. One is a unique version of a gene called EPAS1, which encodes a transcription factor that “turns on hundreds if not thousands of genes in response to low oxygen,” Simonson says.
has revealed that some Andeans, rather than having higher hemoglobin levels, have yet another version of EPAS1—one that, similar to the Tibetan variant, is associated with low hemoglobin and higher oxygen saturation.
“I was surprised to see that EPAS1 was involved,” says Emilia Huerta-Sanchez, a population geneticist at Brown University who wasn’t involved in the new study. In 2014, Huerta-Sanchez and a team of other scientists found that Tibetan highlanders inherited their unique EPAS1 variant from an ancient human subspecies known as Denisovans, who went extinct some 40,000 years ago. The mutation present in modern Quechua people likely arose about 20,000 years later—around the same time that humans first began living in the Andes.
“Whenever we find instances of convergent evolution, especially within a species in two different populations, it’s exciting,” says Tony Capra, a genomics researcher at UC San Francisco who wasn’t involved in the study. Scientists now have “multiple vantage points” to study how natural selection acts on certain high-altitude adaptations, he says.
Simonson notes that the mutations present in Tibetan populations occur in noncoding regions of EPAS1 and have subtle regulatory effects on the expression of the gene in some tissues. The newly discovered variant, however, is “hard coded in the DNA” and could directly impact the structure or function—or both—of the transcription factor in every single cell. That’s “a huge deal,” she explains.
The team also checked large genome databases for signs of the Andean variant. They found it in a few other human populations, but at extremely low frequencies. “The variant is really, really rare and is pretty much nonexistent in the rest of the world,” says study co-author Wanjun Gu, who worked on the project as a member of Simonson’s lab at UC San Diego.
Bizarrely, the only other organism that shares the variant in high frequencies is the West Indian Ocean coelacanth (Latimeria chalumnae)—a rare species of lobe-finned fish that has persisted for hundreds of millions of years. It’s possible that coelacanths may also have evolved the variant as some species adapted to low-oxygen conditions.
PS; When we first landed in Cusco - Peru, which is at an elevation of 3400m which has only about 13% Oxygen in the air we had problems. There were 7 in the group, three couples and my teenaged son. All took the tablets to acclimatize with high altitude with the exception of myself and my son.
All the males were fine but all the females were affected. One of the ladies just climbed one flight of stairs in the hotel, sat down on the landing, my son helped her to the room and she only came out after nearly three hours later for dinner.
While at dinner in the hotel restaurant one NZ lady collapsed at the next table. We helped her out, the hotel handed the oxygen cylinders immediately as they expect these problems. Also the hotel provides Coca Tea 24 hrs which helps you out for altitude sickness.
