Humans have adapted to their different environments over hundreds of thousands of years through a wide variety of behavioral adaptations and genetics. One of the most notable and rapid examples is the genetic changes that have led to high altitude tolerance in populations living in areas like Tibet in southwest China. However, for the majority of humans, high altitude areas are physiologically extremely difficult to inhabit. At 4,000 meters above sea level, each breath of air contains only about 60% of the oxygen found at sea level (Yi et al., 2010). For this reason, altitudes above approximately 7,600 meters become deadly to humans at low altitudes due to the body's hypoxic response to this severe lack of oxygen. Hypoxia is characterized by a number of adverse symptoms, among which the most minor include fatigue, dizziness, shortness of breath, headache, insomnia, malaise, nausea, vomiting, body pain , loss of appetite, ringing in the ears, blisters and dilated veins. . If hypoxia becomes severe enough, cerebral edema (swelling of the brain) or pulmonary edema (fluid buildup in the lungs) can result, as well as excessive breathing leading to extra energy use even at rest, and finally a progressive decrease in heart rate until possible death (Penaloza and Arias-Stella, 2006). Hypoxia is a leading cause of death among mountain climbers, highlighting the extreme consequences that high altitude conditions can have on the average human body (Huey et al., 2001). Say no to plagiarism. Get a tailor-made essay on "Why violent video games should not be banned"? Get the original essay However, instead of experiencing some of these life-threatening symptoms in high-altitude areas, Tibetans are remarkably and skillfully adapted to their otherwise inhospitable environment. environment on “the roof of the world”. Tibetan populations achieve this through various physiological differences from humans living at lower altitudes, such as decreased hemoglobin levels (Yi et al., 2010). Normally, the body increases hemoglobin levels in response to lower oxygen levels in order to increase the affinity of red blood cells for oxygen; however, it can lead to blood clots, strokes, and even death. Tibetans' bodies are adapted to their environment so that this potentially fatal response does not occur (Gibbons, 2014). Furthermore, they resist the normally gradual reduction in birth weight due to altitude; in fact, a progressive increase in birth weight has been observed over the past two decades in these populations. At birth, babies also benefit from better oxygenation to maximize their chances of survival (Yi et al., 2010). Tibetans also breathe faster, inhale more air with each breath, and have enlarged lung volumes to maximize the amount of oxygen reaching their cells. As a result, their exercise capacity is increased. Scientists have even discovered that Tibetan populations naturally have higher levels of nitric oxide in their blood. This helps blood vessels dilate to improve circulation (Beall et al., 2012). A number of genes have conferred this variety of physiological adaptations, one of the most positive and highlyselected being endothelial PAS domain-containing protein 1, or EPAS1. . EPAS1 is a transcription factor involved in the body's response to hypoxia (Yi et al., 2010). It is associated with a slower than normal increase in red blood cell production due to normally hypoxic conditions which, as mentioned above, prevents clots, stroke and death. In addition, a gene called EGLN1 was also highly positively selected in Tibetans, helping to inhibit hemoglobin production under normal oxygen concentration conditions. It also helps prevent clots and strokes. PPARA, when inhibited by the HIF1a transcription factors, is a gene that prevents the typical reduction in red blood cell production in response to high altitudes, thereby helping to maintain red blood cell levels in concert with EPAS1. Together, these three genes function within the broader hypoxia-inducible factor (HIF) pathway. This pathway generally regulates red blood cell production in response to oxygen metabolism and controls red blood cell production (Simonson et al., 2012; Cheviron & Brumfield, 2011). A second collection of genes important in long-term acclimation to altitude that was found near these major "candidate" genes are HBB and HBG2, SPTA1, HFE, FANCA, and PLKR. HBB and HBG2 are associated with a delayed transition from fetal to adult hemoglobin, which would help Tibetans prevent a number of potential hematological diseases due to high altitudes. SPTA1 is associated with red blood cell shape and HFE with iron storage. Finally, FANCA and PLKR are associated with the production and maintenance of red blood cells, respectively (Yi et al., 2010). Since many genes close to each other are inherited together, identifying these nearby genes is useful in determining how Tibetan populations have adapted genetically to their environment. Additionally, women who possess one or two alleles conferring high blood oxygen have also been found to be more likely to give birth to surviving children; these alleles have also been selected for over time (Beall et al., 2004). From extensive genetic analyses, scientists were able to conclude that the EPAS1 allele was acquired from archaic hominins called Denisovans around 40,000 years ago (Huerta-Sánchez et al., 2014). Denisovans are more closely related to Neanderthals than to modern humans and were once present across Asia and into what is now Siberia around 35,000 to 25,000 years ago (Gibbons, 2014; Huerta-Sánchez et al., 2014). Denisova Cave in Siberia, where many Denisova fossils were discovered, was at a high altitude, but not as high as the Tibetan Plateau. However, if the Denisovans had the high-altitude version of EPAS1, the scientists concluded that this could mean that they would have also crossed the more mountainous regions of China and South Asia before spreading across Australia (Huerta-Sánchez et al., 2014). The Tibetan plateau was then colonized around 30,000 years ago by these ancient hominids. This founding population became the broader Han Chinese/Southeast Asian population; the demographics of high-altitude Tibetans began to diverge from those of the Han Chinese and Dai around 40,000 to 20,000 years ago (Jeong et al., 2014). Initially, the Tibetan population was large, but its size declined over time as specific subpopulations became more distinct (Yi et al., 2010). Today, 40.