PH709 The Biology of Public Health

Adaptation refers to the traits that help in survival.  Altitudes above 2500m are considered high altitudes for humans.  The height above sea level affects the flow of blood and pressure in the body causing hypoxia.  High-altitude adaptation in humans involves an evolutionary instance in which humans can withstand high altitudes.  Genomes contribute to the various survival techniques in humans (Hall, 2020).  Higher altitudes are associated with health risks due to the presence of different adverse effects on the normal homeostasis or functioning of the human body as the human body are most reactive stunt to living in low altitude. Therefore, in case of high altitude there is a huge change in the barometric pressure which is associated with the reduced amount of oxygen in the body causing hypobaric hypoxia. 

The sustained effect of hypoxia has diverse effects in the body in multiple ways such as body weight, capacity of exercise, structure of the muscle, functionality of the mind and sleep quality as well (Bigham, 2016). For those that manage to survive in such places, adapt to the altitude levels and reap benefits reported from various researches. While discussing the process of adaptation which can be reported that hyperventilation is the most important step of the process of adaptation and it is mainly gained by hypoxic ventilatory response of the receptors located in the peripheral region.  Such a scenario is evident in specific areas in the continent. Different authors have attempted to explain this phenomenon.  Even though they have a primary aim, some authors have conflicting reports (Storz & Cheviron, 2020). In this essay the reviews the works of the different authors based on the research topic are discussed briefly.

Review of Literature

The authors uniformly agree that high altitude conditions affect barometric pressures that have made humans cope with the lack of oxygen.  The regions known to have humans living in such conditions are the Andean Altiplano, Ethiopian highlands, and the Tibetan plateau. According to Kelsey & Sanchez (2019), and Scheinfeldt & Tishkoff (2010), adaptations to high altitudes are genetically and biologically triggered.  The EPAS1 and EGLN1 genes are linked to the adaptation events.

According to the evidence high altitude can play a major role in the physiological effect of a human being. As per the evidence as the height increase, the level of oxygen becomes low. The main reason for this is low air pressure. The air pressure gets low as the height increase along with the oxygen level. Thus, this low oxygen can cause hypoxia condition to a person (Ortiz-Prado et al., 2019). According to the evidence due to low oxygen, a person can feel increased fatigue and breathing problem (Bigham, 2016). However, people living in the high altitude area, they don’t face such problem. This might be trace back to the genetic alteration of these people for living in a high altitude position for such a long time.

The evidence of genetic changes can be backed up by Bigham, (2016). The author in his research mention, people who live in a high altitude or 2500 m higher than the sea level such as Tibetans, Ethiopians and Andeans does not face symptoms of hypoxia. According to the genetic study author mention, the underlying cause of this adaption is due to the high-altitude adaptive phenotypes. This genetics alteration happens due to the low air pressure. The main components of this alteration are the Hypoxia Inducible Factors (HIF) pathway. HIF is a very old oxygen regulator pathway that mainly regulates the downstream response of hypoxia condition.

40 of this HIF pathways along with some non-HIF genes play an important role in the regulation among Aymara and Andean Quechua. This group of people has HIF genes which as CXCR4, TGFA, NOS2, PRKAA1, and EGLN1. These genes regulate the genetic modification of the hypoxia condition. According to this study author also mention Moreover, Chen et al., (2020) mention people living in high altitude area has a different mitochondrial DNA genomic pattern among different groups. According to this study High-altitude Tajiks (HA-Tajiks) has a major difference in the OXPHOS pathway which is encoded by mtDNA genome compared to Tibetans and Sherpas living in china.

HA-Tajiks have difference in the CYTB, ND5, ND4, ND1, ND2, COX1, ATP8, ATP6, ND3 and ND4L. Author also mentions HA-Tajik has increased linkage of U, H, T and J. Therefore, from this study it can be concluded that different groups of high altitude people may have different gene variation among them. This fact might be trace back to their ancestry. Mairbäurl, Gassmann & Muckenthaler, (2020) mention, geographical ancestry can alter the haemoglobin value of high altitude people. People lives in the high altitude tend to have increased haemoglobin concentration for better oxygen saturation. The analysis of the existing literatures that apart from the genetic variance in different populations living in high altitude area there are a lot of physiological changes in the body of the higher altitude individuals due to living in the higher altitude area.

The physiological alterations due to high altitude living also help the individual to survive in tough environmental conditions as well. High altitude is associated with hypoxic challenge due to enhancing altitude or higher altitude and it is reported that the ambient oxygen pressure gradually decreases causing a drop in the partial pressure of the arterial Oxygen.  As a consequence of this there is a steep drop in the arterial oxygen saturation for sao2.  In order to overcome this alteration in the arterial oxygen content and mentoring the uses of oxygen level in the body, the human body shows different physiological responses (Lundby et al., 2018).  In this regard the enhancement of ventilation over the short term and enhancing red blood cell production in case of long term can be reported.

The long-term altitude responses among the different population groups show different respiratory hematological and circulatory adaptation for surviving in the altitude area (d’Alessandro et al., 2016). The physiological traits of people from the three regions are distinct.  Considering the changes in the different population it can be reported that the resting ventilation is enhanced by 50% among the Tibetan population. In the case of Andean population there is no increase in the resting ventilation. In case of hypoxic ventilatory response the Andean population showed decrease and in case of Tibetan population graph hypoxic ventilatory response  remains the same. The Tibetan population showed no change in case arterial oxygen saturation level and on the other hand both Ethiopian population and Andean  population showed elevation. 

The Ethiopian Population and Tibetan population had minimal increase in case of hemoglobin concentration in high altitude conditions compared to the elevated level of hemoglobin concentration in case of Andean population. The pulmonary arterial pressure is elevated in the high altitude conditions among Andean population and Ethiopian population and in case of Tibetian population there is a minimal increase in the pulmonary arterial pressure. Tibetans have a high resting ventilation, but low oxygen levels in the arteries (Yang, 2017).  The Andes population has shown normal resting ventilation, high hemoglobin concentration, and increased oxygen content in arteries (Julian & Moore, 2019).  Jacovas, Couto, & Nunes (2018) suggest that three new genes have recently been found, to be associated with high-altitude adaptations among the Andeans. 

Using selection evidence, the SP100 and DUOX2 genes were found to exist in the hypoxia routes.  These genes lead to adaptations in skeletal muscles and immune functions among the unborn.  Ethiopians have no physiological response to high altitude, but show an increase in hemoglobin and respiration, for those living in low-altitude areas. This finding was also supported by the study of Jacovas et al. (2018). In study the researchers reported the association of the above-mentioned genes in the case of Andean population grouped residing in high altitude areas.

In this study it was reported that the expression of sp100 gene is higher in the skeletal muscles of the Andean population group and this expression is associated with the HIF pathway. One of the members of the HIF pathway named HIF-1 plays a significant role in the controlling of oxygen homeostasis which is related to the heart muscle and skeletal muscle adaptations in the reduced oxygen supply in the higher altitude area (Bigham & Lee, 2014). 

Therefore, it is reported that the presence of HIF-1 can help in the process of adaptation during reduced muscle mass and overall physiological performance in absence of adaptation.  Moreover, the presence of HIF-1 also helps in the process of cell survival during the lower amount of oxygen delivery to the cells and tissues and it mainly exerts its action against the p53 that promotes the cell death during hypoxia condition.

In normal conditions the level of p53 and HIF-1 is low and along with the progression of mild hypoxia the level of p53 starts to increase in a slow rate compared to the higher progression level of HIF-1. On the contrary to the situation during the severe level of hypoxia the p53 is accumulated in higher concentration by suppressing the accumulation of HIF-1 which leads to the destruction of healthy cells by the process of apoptosis.  In case of adaptation the higher level of HIF-1 Is reported in the cells and hence in spite of p53 accumulation the cells manage to survive in low oxygen condition as well.

Another crucial physiological response in case of high altitude it can be reported that the landers show an immediate increase in the ventilation name as hypoxic ventilatory response or HVR. However, this short term high altitude exposure is not continued in case of long-term exposure and the resting ventilation comes back to the lower altitude level after a few days of living in the high altitude area (Gonzales, Alarcón-Yaquetto & Zevallos-Concha, 2016).

Along with HVR, another important physiological component that is affected by the higher altitude is the maximal oxygen consumption for vo2 Max.  Vo2 max refers to the apartment capacity of the individuals to transport and use oxygen during performing any exercise which also shows the physical capability of the individual.  While discussing the impact of high altitude in individuals it can be reported that the Vo2 Max starts to decrease above the altitude of 1600m and after that the Vo2 max is reduced by 8-11% in case of every 1000 metre rise in the altitude. For example, it can be reported that at the Summit of Everest the Vo2 Max can drop to 15 ml/Kg/min from 62 mL/kg/min. So, an individual with a Vo2 max of less than 50ml/kg/min would face serious respiratory complications at the Summit of Everest (Venkat, Dhillon & Rowley, 2021). 

Among the long-term effects of exposure to high altitudes, is living with chronic mountain sickness (CMS), also known as Monge’s disease; having symptoms such as pulmonary and peripheral edema (Azad,  2017). Considering the issue of CMS it can be reported that the cases of CMS vary with the age, sex altitude and generational time of residence. In this context it can be reported that the valence of CMS is higher among the populations with low multigenerational residence at higher altitude areas. For example the Han population in Himalayas Rocky Mountain population in Colorado can be mentioned. and on the other and the prevalence is low among the population having greater multigenerational residence at high altitude areas.  Along with this the living in high altitude areas is also associated with lower birth weight and greater child mortality rate. It is also very important to mention that the higher maternal hemoglobin concentration can reduce the fetal growth at higher altitude area and for example a hemoglobin concentration value of more than 14.5 gram/dL can affect the birth weight of the children in a negative manner.

The study of Lane et al. (2020),  reported that the foetal growth is protected by the presence of greater uterine artery blood flow among the Andeans at higher altitude area and in case of lower uterine blood flow the early onset of pre-eclampsia can be reported that is associated with fetal hypoxia and higher maternal hemoglobin level.  Other effects include stress on the cardiopulmonary system.  The adaptations developed by humans in such areas include vascular responses, higher resting ventilation; maintenance of high blood flow in the uterine artery; increased blood count of red blood cells; and increased concentration of hemoglobin (Crawford,, 2017).

Although Moore (2017), agrees with the decrease in oxygen, she differs from the rest by saying genetics also improves metabolism and oxygen delivery.  O'Brien et al., (2020) supports her; by saying that high altitudes have a significant impact on remodeling metabolic tissues.  She also adds a fourth region associated with high-altitude adaptations, the Rocky Mountains in North America, inhabited for lesser years than the other regions.  Although, adaptations are genetically influenced as illustrated by other authors, she points out that the notion can be misleading, because some adaptations may occur after the natural selection had long occurred for individuals with no genetic history.  Another area of conflict evaluating adaptations, is based on characteristics such as the amount of oxygen.  The researcher argues that the assumption is analogous and that evidence of natural selection must be used to determine adaptations instead of characteristics.

Conclusion

Hence, it can be concluded that the high altitude condition is associated with different changes in the body of the human beings and these changes help the human beings to survive in the tough environmental conditions as well. Physiological and genetic adaptations are seen in humans, who have lived in high-altitude environments for generations.  Only three regions, are found to have people which have adapted to such environments.  Despite their common characteristic of adaptability, the adaptations differ among the three communities. People living in high altitude areas have a different mitochondrial DNA genomic pattern among different groups. According to this study High-altitude Tajiks (HA-Tajiks) has a major difference in the OXPHOS pathway which is encoded by mtDNA genome compared to Tibetans and Sherpas living in china.

Ambient oxygen pressure gradually decreases causing a drop in the partial pressure of the arterial Oxygen.  As a consequence of this there is a steep drop in the arterial oxygen saturation for sao2. the enhancement of ventilation over the short term and enhancing red blood cell production in case of long term can be reported. The long-term altitude responses among the different population groups show different respiratory hematological and circulatory adaptation for surviving in the altitude area.  Some, of the adaptations may pose health risks, but can also be beneficial in metabolism, according to some of the authors.  The contradiction in the measuring factors, affects my research topic; which will require additional research on other characteristics; that can be used to classify adaptability to high-altitude areas.

References

Azad, P., Stobdan, T., & Haddad, G. (2017). High-altitude adaptation in humans: From genomics to integrative physiology. Journal of Molecular Medicine, 126-1282. https://doi.org/10.1007/s00109-017-1584-7

Bigham, A. W. (2016). Genetics of human origin and evolution: high-altitude adaptations. Current opinion in genetics & development, 41, 8-13. Retrieved from https://doi.org/10.1016/j.gde.2016.06.018

Bigham, A. W., & Lee, F. S. (2014). Human high-altitude adaptation: forward genetics meets the HIF pathway. Genes & development, 28(20), 2189-2204. http://genesdev.cshlp.org/content/28/20/2189.short

Chen, Y., Gong, L., Liu, X., Chen, X., Yang, S., & Luo, Y. (2020). Mitochondrial DNA genomes revealed different patterns of high-altitude adaptation in high-altitude Tajiks compared with Tibetans and Sherpas. Scientific reports, 10(1), 1-9. Retrieved from https://doi.org/10.1038/s41598-020-67519-z

Crawford, J., Amamru, R., Moore, L., Song, J., Prchal, J., & Nielsen, R. (2017). Natural selection on genes related to cardiovascular health in high-altitude adapted Andeans. American Journal of Human Genetics, 752-767. https://doi.org/10.1016/j.ajhg.2017.09.023

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Gonzales, G. F., Alarcón-Yaquetto, D. E., & Zevallos-Concha, A. (2016). Human adaptation to life at high altitude. Biochemistry of Oxidative Stress, 109-126. https://link.springer.com/chapter/10.1007/978-3-319-45865-6_8

Hall, J., Lawrence, E., Monson, T., & Fox, K. (2020). Seq-ing higher ground: Functional investigation of adaptive variation associated with high-altitude adaptation. Frontiers in Genetics, 471. https://doi.org/10.3389/fgene.2020.00471

Jacovas, C., Couto, M., & Nunes, K. (2018). Selection scan reveals three new loci related to high altitiude adaptation in Native Andeans. Sci Rep 8. https://doi.org/10.1038/s41598-018-31100-6

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Julian, C., & Moore, L. (2019). Human genetic adaptation to high altitude: Evidence from the Andes. In Genes. https://doi.org/10.330/genes10020150

Kelsey, W., & Sanchez, E. (2019). Convergent evolution in human and domesticate adaptation to high-altitude environments. doi:http://doi.org/10/108/rstb.2018.02

Lane, S. L., Doyle, A. S., Bales, E. S., Lorca, R. A., Julian, C. G., & Moore, L. G. (2020). Increased uterine artery blood flow in hypoxic murine pregnancy is not sufficient to prevent fetal growth restriction. Biology of reproduction, 102(3), 660-670. https://academic.oup.com/biolreprod/article-abstract/102/3/660/5618863

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O'Brien, K., Simonson, T., & Murray, A. (2020). Metabolic adaptation to high altitude. Current Opinion in Endocrine and Metabolic Research, 33-41. https://doi.org/10.1016/j.coemr.2019.12.002

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Venkat, D., Dhillon, K., & Rowley, J. A. (2021). Effects of High Altitude on Sleep and Respiratory System. Current Pulmonology Reports, 1-7. https://www.hindawi.com/journals/tswj/2013/241569/

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