By Tenzin Kunsang, Jones College Prep, Chicago, IL
Tibet, a linkage between two of the world’s most populous countries, sits high at an altitude of about 4,380 meters. For reference, New York City’s highest elevation is 125 meters (USGS, 1995), and Mt. Everest—the tallest mountain in the world—is 8,850 meters tall (Rutledge, 2011). Indigenous Tibetans have evolved with adaptations that allow for them to live more than 4,000 meters above sea level, an altitude that others might find sickening and unbearable to live in.
If a person from a low land area travels to high altitudes, their body typically responds by making more hemoglobin, a protein that carries oxygen by binding to red blood cells (RBCs). Hemoglobin acts at a higher level to compensate for the lack of oxygen in the air, but an excess of hemoglobin may cause altitude sickness. Indigenous Tibetans, however, have the adaptations that allow them to survive at such high altitudes, while also maintaining low hemoglobin levels (Live Science Staff, 2010).
Curious about how Tibetans gained these adaptations, Case Western University’s Cynthia Beall collected blood samples from nearly 200 Tibetan villagers living in three high altitude regions in the Himalayas. When comparing DNA of Tibetan villagers to those of low landers, the EPAS1 gene—a gene that catalyzes red blood cell production and, therefore, increases hemoglobin concentration—on chromosome 2, was seen to differ between the two populations. Although this gene is universal to all humans, mutations had occurred at the locus, which gave the people living atop the Tibetan plateau an evolutionary advantage to survive and reproduce, which is the primary goal for all organisms (Live Science Staff, 2010). But why repress a gene that codes for a protein essential for survival in thin air? Hemoglobin adds to blood’s viscosity, which results in “compromised oxygen delivery to tissues and cerebrovascular complications” (Yip, 2000). Therefore, Tibetans have evolved to use RBCs effectively and efficiently.
Another researcher, Rasmus Nielsen, from the University of California, Berkeley, found that a staggering 87% of Tibetans and a mere 9% of Han Chinese possessed the EPSA1 mutation even though they had only speciated less than 3,000 years ago. The stark difference between the two populations exemplifies how the environment contributes to the process of evolution.
When these genes are compounded with other mutations such as a mutation in ADH7 which results in a higher BMI and ability to store energy at high elevations or a mutation in HLA-DBQ1 which distinguishes foreign proteins from the body's innate proteins, it causes Tibetans to be able to live at higher altitudes than the average individual (Price, 2017).
There is a drawback to these adaptations, however. According to the World Health Organization (WHO), anemia is defined as a blood hemoglobin concentration below 120 g/L. When anemic, people often experience shortness of breath, fatigue, dizziness, headaches, irregular heartbeat, and organ damage (National Institutes of Health, 2011). When WHO sampled 480,699 women from 10 ethnic minorities in China, the organization found that Tibetans had the highest anemia rate (46.9%). The high rate of anemia is most likely caused by the hypoxic environment atop the Tibetan plateau (Zhang et. al, 2017). Anemia occurs when an individual has lower than normal hemoglobin levels because of a lack of RBCs (The American, 2020). Tibetans living at high altitudes have evolved to regulate hemoglobin levels in a hypoxic environment, which means they produce fewer RBCs than a typical individual, translating to higher susceptibility to anemia.
Science writer Ed Yong describes the distinct biological features of Tibetans as “the strongest instance of natural selection documented in a human population” (Yong, 2014). Although a benefit, these distinctions also make the Indigenous Tibetan population and their descendants vulnerable to anemia. The predisposition to a lack of RBCs is not limited to Tibetans but to all populations living at high altitudes, such as Bolivians and the Bhutanese. Regardless, the pros and cons of limited hemoglobin production only broaches the idea of evolutionary trade-offs and their effect on a population.
“The distribution of hemoglobin concentration among Tibetan men at 3932m (left panel), women (right panel). Solid vertical lines indicate the current WHO hemoglobin concentration thresholds for anemia adjusted for age and sex; the dashed vertical lines indicate the current WHO thresholds adjusted for age, sex, and altitude” (Sarna, 2020).
References
Eastern Region Geography, I. (1995). Elevations and Distances in the United States. Retrieved July 13, 2020, from https://pubs.usgs.gov/gip/Elevations-Distances/elvadist.html
Kelly, M. (2013, July 1). Altitude sickness may hinder ethnic integration in the world's highest places. Retrieved July 13, 2020, from https://www.princeton.edu/news/2013/07/01/altitude-sickness-may-hinder-ethnic-integration-worlds-highest-places
Luksenburg, Harvey. “Iron-Deficiency Anemia.” Womenshealth.gov, Office on Women's Health, 1 Apr. 2019, www.womenshealth.gov/a-z-topics/iron-deficiency-anemia#:~:text=If%20left%20untreated%2C%20iron%2Ddeficiency,work%20can%20harm%20the%20heart.
Price, M. (2017, July 26). Mutations may reveal how Tibetans can live on world's highest plateau. Retrieved July 13, 2020, from https://www.sciencemag.org/news/2017/04/mutations-may-reveal-how-tibetans-can-live-world-s-highest-plateau
Rutledge, K., Ramroop, T., Boudreau, D., McDaniel, M., Teng, S., Sprout, E., . . . Hunt, J. (2012, October 09). Altitude. Retrieved July 13, 2020, from https://www.nationalgeographic.org/encyclopedia/altitude/
Sarna, K., Brittenham, G., & Beall, C. (2020, March 04). Current WHO hemoglobin thresholds for altitude and misdiagnosis of anemia among Tibetan highlanders. Retrieved July 13, 2020, from https://onlinelibrary.wiley.com/doi/full/10.1002/ajh.25765
Staff, L. (2010, June 07). Revealed: How Tibetans Survive Thin Air. Retrieved July 13, 2020, from https://www.livescience.com/6543-revealed-tibetans-survive-thin-air.html
The American Cancer Society medical and editorial content team(2020, February 1). Low Red Blood Cell Counts (Anemia). Retrieved July 13, 2020, from https://www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects /low-blood-counts/anemia.html
Yip, R. (2000, July 01). Significance of an abnormally low or high hemoglobin concentration during pregnancy: Special consideration of iron nutrition. Retrieved July 13, 2020, from https://academic.oup.com/ajcn/article/72/1/272S/4729661
Yong, E. (2014, July 02). Extinct Humans Passed High-Altitude Gene to Tibetans. Retrieved July 13, 2020, from https://www.nationalgeographic.com/science/phenomena/2014/07/02/sex-with-extinct-hum ans-passed-high-altitude-gene-to-tibetans/
Zhang, X., He, Y., Xie, X., Ji, M., Ma, X., & Yu, Z. (2017, December). Distribution of hemoglobin and prevalence of anemia in 10 ethnic minorities in China: A population-based, cross-sectional study. Retrieved July 13, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5815799/