Tibetan High Altitude Adaptation PDF

Adaption to high Altitude in Tibetans Anna Derrick [email protected]  Exam Instructions 75% weighting There are 50 multi choice questions covering all aspects of this module. The exam is time-limited to 1 hour (unless you have been granted extra time on the system). One...

Adaption to high Altitude in Tibetans Anna Derrick [email protected]  Exam Instructions 75% weighting There are 50 multi choice questions covering all aspects of this module. The exam is time-limited to 1 hour (unless you have been granted extra time on the system). One question will be displayed at a time and you will not be able to go back to view previous questions. A Single Best Answer format with Negative Penalty Marking will be used: Students have five answer choices and pick the ONE CORRECT answer (+4 marks) but receive negative marks (-1 mark) for choosing an incorrect answer, so that pure guessing is not rewarded. The system will only let you make one choice (or no choices if you wish, scoring 0 marks for that question). If you have any problems when completing the exam, please take a screenshot (with time stamp) of the issue and contact [email protected] Timetable will be published w/c 27th November 2023. This will be available to view via your student Intranet account.  Quiz Test your knowledge from last lecture! (Sickle Cell Disease) https://kahoot.it Also available on: Learning Outcomes Understand how high altitudes affect the human body. Recognise the differences between acclimatisation and adaptation. Describe how Tibetan people have physiologically adapted to high altitude living and the genes implicated. Altitude - Oxygen Higher the altitude lower the Partial Pressure of Oxygen (PO2) in this air.  Altitude Oxygen PO2 Altitude – PO2 (feet) level (mmHg) 30,000 32% 51 Death Zone 26,000 25,000 39% 62 20,000 48% 73 15,000 58% 92 10,000 70% 110 Rapid decrease 6,900 5,000 84% 134 Sea Level 100% 159  PO2 Altitude Altitude (feet) Oxygen content mmHg 30,000 32% 51 Mount Everest – 29,031ft 26,000 Ultra 25,000 39% 62 Aconcagua – 22,838ft Denali – 20,310ft 20,000 Extreme 48% 73 Kilimanjaro – 19,341ft Mont Blanc – 15,774ft 15,000 58% 92 Very High 10,000 70% 110 High 6,900 5,000 84% 134 Ben Nevis – 4,413ft Snowdon – 3,560ft Medium Pen y Fan – 2,907ft Sea Level 100% Low 159 High-altitude hypoxia Hypoxia - deficiency in the amount of oxygen reaching the tissues. PaO2 = Arterial partial pressure of oxygen SaO2 = Oxygen saturation High-altitude hypoxia – Initial Physiological Response Increase respiration rate. Increase heart rate. Respiratory alkalosis: Decreases in CO2 elevates the blood pH. Acute altitude sickness: Dizziness, nausea, fatigue, and headaches. Acclimatise Changes to an organisms behaviour, morphology and physiology in response to a unique environment. Phenotypic plasticity It is NOT a genetic change. High-altitude Acclimatisation Low PaO2 and SaO2 Erythropoiesis Erythropoietin. Increase oxygen to tissue. Compensate for decreased oxygen levels. Long-term sustained high-altitude hypoxia Develop a maladaptation syndrome: Chronic mountain sickness Pulmonary hypertension High-altitude pulmonary edema High-altitude cerebral edema Heart failure Fetal intrauterine growth restriction. Tibet altitude Tibet altitude  Average altitude by country Tibetan People Population = 3.6 million  Physiological adaptions of Tibetans Lower infant mortality and higher fertility than acclimated women of low-altitude origin. Protection against the occurrence of intrauterine growth restriction, which is associated with low birth weight at high altitude. Protection against preeclampsia which is associated acclimated women of low-altitude origin. Petousi.N , et al. (2014) Human adaptation to the hypoxia of high altitude: the Tibetan paradigm from the pregenomic to the postgenomic era. Journal Applied Physiology, 116(7):875-84. Physiological adaptions of Tibetans Protection against erythrocytosis. Have a standard haemoglobin concentration (opposite to acclimatation). Petousi.N , et al. (2014) Human adaptation to the hypoxia of high altitude: the Tibetan paradigm from the pregenomic to the postgenomic era. Journal Applied Physiology, 116(7):875-84.  Physiological adaptions of Tibetans Decreased homocysteine levels, possibly due to increased folate acid metabolism. Protection against cardiovascular disease. Low weight and body mass Genome studies Tibetans Han Chinese In just 3000 years the Tibetan people have rapidly evolved a unique ability to thrive at high altitudes and low oxygen levels The fastest genetic adaption ever observed in humans Genome studies Genome wide association study (GWAS) - strongest signatures of positive selection: EGLN1 and EPAS1 Zheng.W, et al. (2023) Large-scale genome sequencing redefnes the genetic footprints of high-altitude adaptation in Tibetan. Genome Biology, 24:73 Genome studies TBN - Tibetan CHB - Han Chinese JPT - Japanese CEU - European YRI - Yoruba EPAS1 - NM_001430.4:c.779+803C>T EGLN1 - NM_022051.2:c.12C>G, NP_071334.1:p.Asp4Glu Zheng.W, et al. (2023) Large-scale genome sequencing redefnes the genetic footprints of high-altitude adaptation in Tibetan. Genome Biology, 24:73 High Altitude Genetic Adaption - EPAS1 gene Endothelial PAS domain-containing protein 1 (EPAS1) Provides instructions for making a protein called hypoxia-inducible factor 2-alpha (HIF-2α). A transcription factor involved in the physiological response to oxygen concentration. The gene is active under hypoxic conditions. Petousi.N , et al. (2014) Human adaptation to the hypoxia of high altitude: the Tibetan paradigm from the pregenomic to the postgenomic era. Journal Applied Physiology, 116(7):875-84.  High Altitude Genetic Adaption - EGLN1 gene Egl nine homolog 1 (EGLN1). Encodes the enzyme - Hypoxia-inducible factor prolyl hydroxylase 2 (PHD2). Central role in oxygen homeostasis as a cellular oxygen sensor. Under normal oxygen levels it catalyses the post-translational formation of 4- hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Graham.A.M, et al., (2018) Convergent evolution on the hypoxia-inducible factor (HIF) pathway genes EGLN1 and EPAS1 in high-altitude ducks. Heredity, 122(6): 819–832. I hope you enjoyed the module and its just the beginning of your interest in different populations across the world.