image:
People who visit the Andes Mountain Range in South America can feel the physical effects of lower oxygen levels at higher altitudes. However, some people who live there have evolved over hundreds of generations to tolerate these low-oxygen conditions.
Credit: Elysia Cook McDermott
Humans are still evolving, and Tatum Simonson, PhD, founder and co-director of the Center for Physiological Genomics of Low Oxygen at University of California School of Medicine, plans to use evolution to improve healthcare for all.
Her latest research, which was published February 9, 2024 in Science Advances, reveals that a gene variant in some Andean people is associated with reduced red blood cell count at high altitude, enabling them to safely live high in the mountains in low-oxygen conditions. Simonsons UC San Diego lab is applying those findings toward understanding whether there may be a genetic component to why some people with sleep apnea or pulmonary diseases such as chronic obstructive pulmonary disease (COPD) fare better than others.
Explained Simonson, There are people with COPD who breathe a lot and maintain a higher oxygen saturation. Others with the same disease don't breathe as much, and their oxygen saturation is low. Researchers suspect there may be genetic differences underlying this variation, similar to the variation we find in pathways important for oxygen sensing and responses underlying natural selection at high altitude.
Our cells need oxygen to survive. When there isnt enough in the environment, our bodies produce extra red blood cells, which transport oxygen throughout the body. Too many red blood cells, however, create a dangerous condition called excessive erythrocytosis (EE), which makes the blood viscous, which could lead to stroke or heart failure.
Her previous research showed that many mountain-dwelling Tibetans exposed to low-oxygen situations are born with innate mechanisms that protect them from poor outcomes at high altitude, including the overproduction of red blood cells. Part of this is due to changes in the regulation of the EPAS1 gene, which lowers hemoglobin concentrations by regulating the pathway that responds to changing oxygen levels. Advances in genetics have shown that modern Tibetans received this genetic advantage from their ancestors who mixed with archaic humans living in Asia tens of thousands of years agoa unique evolutionary history confined to this population.
For her latest research, Dr. Simonson, who is also the John B. West Endowed Chair in Respiratory Physiology and associate professor in the Division of Pulmonary, Critical Care, Sleep Medicine & Physiology at UC San Diego School of Medicine, zoomed in on the EPAS1 region of the genome. She and her team focused on a mutation in the gene that is present in some people living in the Andes but is absent in all other human populations. When they scanned whole Andean genomes, they found a pattern surrounding this variant suggesting that the genetic change, which alters only a single amino acid in the protein product, happened by chance, relatively recently (from 9,000 to 13,000 years ago), and spread very quickly through hundreds of generations within the Andean population.
Similar to Tibetans, the EPAS1 gene is associated with lower red blood cell count in Andeans who possess it. However, the researchers were surprised to find that the variant works in a completely different way from the Tibetan version of the gene; rather than regulating its levels, the Andean variant changes the genetic makeup of the protein, altering the DNA in every single cell.
Tibetans have, in general, an average lower hemoglobin concentration, and their physiology deals with low oxygen in a way that doesnt increase their red blood cells to excessively high levels. Now we have the first signs of evidence that Andeans are also going down that path, involving the same gene, but with a protein-coding change. Evolution has worked in these two populations, on the same gene, but in different ways, said Simonson.
This study exemplifies a current approach in research that connects genetic targets of natural selection with complex disease genesunderstanding, for example, how natural genetic variation contributes to adaptive and maladaptive responses to low oxygen, as this study reveals.
In Simonsons lab, that means figuring out what downstream target genes are being turned on in response to low oxygen, among other things. Said Simonson, This paper shows one gene associated with one particular phenotype, but we think there are many different genes and components of oxygen transport involved. Its just one piece of that puzzle, and could provide researchers with information relevant to other populations.
Simonson and her team are working with Latino populations in San Diego and El Centro, California, as well as Tijuana and Ensenada, Mexico, taking them to high altitudes and recording their breathing while awake and asleep. Theyre cross-referencing their findings with publicly available databases to determine whether the findings theyve made in Andeans are also found in local Latinos who may share some genetic variants with the Andeans.
In precision medicine, its important to recognize variation in genetic backgrounds, specifically in historically understudied populations, Simonson said. If we can find some shared genetic factors in populations in an extreme environment, that may help us understand aspects of health and disease in that group and groups more locally. In that way, this study aims to push research forward, and towards comprehensive personalized medicine approaches in clinics here in San Diego.
Co-authors of the study include: Elijah S. Lawrence, Wanjun Gu, James J. Yu, Erica C. Heinrich, Katie A. OBrien, Carlos A. Vasquez, Quinn T. Cowan , Patrick T. Bruck , Kysha Mercader, Mona Alotaibi, Tao Long, James E. Hall, Esteban A. Moya, Marco A. Bauk, Jennifer J. Reeves, Mitchell C. Kong, Rany M. Salem, Keolu P. Fox, Atul Malhotra, Frank L. Powel, Mohit Jain and Alexis C. Komor at UC San Diego, Ryan J. Bohlender, Hao Hu and Chad D. Huff at University of Texas MD Anderson Cancer Center, Cecilia Anza-Ramirez, Gustavo Vizcardo-Galindo , Jose-Luis Macarlupu , Rmulo Figueroa-Mujca, Daniela Bermudez, Noemi Corante and Francisco C. Villafuerte at Universidad Peruana Cayetano Heredia, Eduardo Gaio at Universidad de Braslia, Veikko Salomaa and Aki S. Havulinna at Finnish Institute for Health and Welfare and Andrew J. Murray at Cambridge University and Gianpiero L. Cavalleri at Royal College of Surgeons in Ireland.
This study was funded, in part, by the National Institutes of Health (Grants R01HL145470 [TSS] and T32HL134632 [JEH]), Geographic Society Explorer Award, and John B West Endowment in Respiratory Physiology (TSS), Wellcome Trust Award 107544/Z/15/Z (FCV), Marie Skodowska-Curie grant agreement No 890768 (KAO), National Academies of Sciences, Engineering, and Medicine Ford Foundation Fellowship (CAV), National Science Foundation Grant No DGE-2038238 (PTB), Research Corporation for Science Advancement through Cottrell Scholar Award 27502 (ACK), Science Foundation Ireland 12/IP/1727 (GLC), Finnish Foundation for Cardiovascular Research and Juho Vainio Foundation (VS), and Academy of Finland (ASH).
# # #
Alexis Komor is a member of the SAB of Pairwise Plants, is an equity holder for Pairwise Plants and Beam Therapeutics, and receives royalties from Pairwise Plants, Beam Therapeutics, and Editas Medicine via patents licensed from Harvard University. Mohit Jain and Tao Long are affiliated with Sapient Bioanalytics, LLC.
Read more:
Harnessing human evolution to advance precision medicine - EurekAlert
- Introgression and disruption of migration routes have shaped the genetic integrity of wildebeest populations - Nature.com - April 15th, 2024 [April 15th, 2024]
- Is Left-Handedness Tied to Your Genetics? Possibly, New Study Suggests - Technology Networks - April 15th, 2024 [April 15th, 2024]
- A pan-genome of 69 Arabidopsis thaliana accessions reveals a conserved genome structure throughout the global ... - Nature.com - April 15th, 2024 [April 15th, 2024]
- Clemson researchers pave the way for precision medicine with AI - Clemson News - April 15th, 2024 [April 15th, 2024]
- ACMG Foundation for Genetic and Genomic Medicine Elects Four Highly Accomplished Medical Genetics ... - PR Newswire - April 15th, 2024 [April 15th, 2024]
- Katie Gallagher MS '15, CGC Named Director of the Joan H. Marks Graduate Program in Human Genetics at Sarah ... - Sarah Lawrence College - April 15th, 2024 [April 15th, 2024]
- The genomic architecture of inherited DNA variants - Baylor College of Medicine | BCM - April 15th, 2024 [April 15th, 2024]
- Clemson genetics major named Truman Scholar for her work in combatting rare diseases - ABC NEWS 4 - April 15th, 2024 [April 15th, 2024]
- Otago University Discovers Cause of Rare Genetic Condition - Mirage News - April 15th, 2024 [April 15th, 2024]
- Genetic Analysis Guides Conservation of Endangered Bumble Bee - Entomology Today - April 15th, 2024 [April 15th, 2024]
- First insights into the genetic bottleneck characterizing early sheep husbandry in the Neolithic period - EurekAlert - April 15th, 2024 [April 15th, 2024]
- Protein-truncating variants in BSN are associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease - Nature.com - April 7th, 2024 [April 7th, 2024]
- A deep dive into the genetics of alcohol consumption - Medical Xpress - April 7th, 2024 [April 7th, 2024]
- Right-wing authoritarianism appears to have a genetic foundation - PsyPost - April 7th, 2024 [April 7th, 2024]
- UC Irvine-led research team builds first tandem repeat expansions genetic reference maps - UCI News - April 7th, 2024 [April 7th, 2024]
- A Deep Dive Into the Genetics of Alcohol Consumption - University of California San Diego - April 7th, 2024 [April 7th, 2024]
- Untold story of bird evolution revealed through genetics - Earth.com - April 7th, 2024 [April 7th, 2024]
- Genetic Test for Opioid Addiction Risk Should Be Withdrawn, Experts Tell FDA - Medpage Today - April 7th, 2024 [April 7th, 2024]
- Scientists Discover 17 New Genetic Variants Linked to Alzheimer's Disease - SciTechDaily - April 7th, 2024 [April 7th, 2024]
- An hereditary liver disease cured with the help of gene scissors - EurekAlert - April 7th, 2024 [April 7th, 2024]
- World Anthropology Day showcases multifaceted programs | Binghamton News - Binghamton University - April 7th, 2024 [April 7th, 2024]
- Resilience to periodic disturbances and the long-term genetic stability in Acropora coral | Communications Biology - Nature.com - April 7th, 2024 [April 7th, 2024]
- Rare genetic variants found to have a large impact on obesity risk - Drug Target Review - April 7th, 2024 [April 7th, 2024]
- INTERACT COALITION FORMED TO ADVANCE PATIENT ACCESS TO GENETIC TESTING FOR HEREDITARY ... - PR Newswire - April 7th, 2024 [April 7th, 2024]
- Christensen Genetics - AG INFORMATION NETWORK OF THE WEST - AGInfo Ag Information Network - April 7th, 2024 [April 7th, 2024]
- New form of EDS identified by mutation in THBS2 gene - Ehlers-Danlos News - April 7th, 2024 [April 7th, 2024]
- Genetics of estrogen production linked to endometrial cancer risk in postmenopausal women - News-Medical.Net - February 13th, 2024 [February 13th, 2024]
- Cord Blood Registry (CBR) by CooperSurgical and Fulgent Genetics Launch Innovative Genetic Testing - PR Newswire - February 13th, 2024 [February 13th, 2024]
- Gene Variant Linked to Lower Levels of Hormonal Birth Control - The Scientist - February 13th, 2024 [February 13th, 2024]
- CooperSurgical, Fulgent partner on genetic screening panels - Medical Device Network - February 13th, 2024 [February 13th, 2024]
- UM Today | Faculty of Science | The intersection of genetics and advocacy - UM Today - February 13th, 2024 [February 13th, 2024]
- Genome-wide association study identifies human genetic variants associated with fatal outcome from Lassa fever - Nature.com - February 13th, 2024 [February 13th, 2024]
- Secrets of human genetics could optimize medical care - Earth.com - February 13th, 2024 [February 13th, 2024]
- Significance of genetic mutations in toxic tort cases - Rhode Island Lawyers Weekly - February 13th, 2024 [February 13th, 2024]
- Why Should Farmers Invest in New Genetics? A Recent Panel Discussion Offered Some Good Reasons - Seed World - February 13th, 2024 [February 13th, 2024]
- The Role of Genetics and Maternal Factors in Retinopathy of Prematurity: A Comparative Study - Medriva - February 13th, 2024 [February 13th, 2024]
- 'The Idea That Who You Are Is Only Genetics Is the Essence of Evil' - Books - Haaretz - February 13th, 2024 [February 13th, 2024]
- IPK researchers provide genetic explanations for shade-induced biomass allocation in wheat - EurekAlert - February 13th, 2024 [February 13th, 2024]
- River Valley Beef Cattle Conference to explore state of hay availability, cattle genetics and more - Stuttgart Daily Leader - February 13th, 2024 [February 13th, 2024]
- Twins are a mirror to each other and a window into the mysteries of genetics - WAMU 88.5 - February 13th, 2024 [February 13th, 2024]
- Unveiling the Disparity in Cardiovascular Health: Biological Factors, Dyslipidemia, and Genetics - Medriva - February 13th, 2024 [February 13th, 2024]
- Parental traits offer new clues to predicting neurodevelopmental disorders in children - News-Medical.Net - February 13th, 2024 [February 13th, 2024]
- Cheetahs Are Extremely Inbred: 50 Interesting Genetics Facts You May Have Missed At School - Bored Panda - February 4th, 2024 [February 4th, 2024]
- Five Best: Books on Genetics - WSJ - The Wall Street Journal - February 4th, 2024 [February 4th, 2024]
- 4 new US sites added to global Parkinson's genetics study - Parkinson's News Today - February 4th, 2024 [February 4th, 2024]
- Animal Genetics Market revenue to exceed USD 43.4 Billion by 2036, says Research Nester - Yahoo Finance - February 4th, 2024 [February 4th, 2024]
- Nobel Laureate and World-Renowned Geneticist to Speak at 2024 Commencement - News Center - Feinberg News Center - February 4th, 2024 [February 4th, 2024]
- Efforts are underway to improve genetics in cattle herds to better sustainability - RFD-TV - February 4th, 2024 [February 4th, 2024]
- First report on the molecular phylogenetics and population genetics of Aedes aegypti in Iran - Parasites & Vectors - Parasites & Vectors - February 4th, 2024 [February 4th, 2024]
- What can your DNA say about your risk of opioid addiction? - National Geographic - February 4th, 2024 [February 4th, 2024]
- The Born in Guangzhou Cohort Study enables generational genetic discoveries - Nature.com - February 4th, 2024 [February 4th, 2024]
- Invitae Partners with BridgeBio Pharma to Harness Genetic Insights for the Discovery of Rare Disease Therapeutics - PR Newswire - February 4th, 2024 [February 4th, 2024]
- Rare disorder causing extra fingers and toes identified - EurekAlert - February 4th, 2024 [February 4th, 2024]
- Retinal OCT and Genetics Identify Links Between Ocular and Systemic Health - Photonics.com - February 4th, 2024 [February 4th, 2024]
- Researchers discover mechanism that protects tissue after faulty gene expression - News-Medical.Net - February 4th, 2024 [February 4th, 2024]
- Genetics or lifestyle: What makes the greatest difference in health? - Agweek - February 4th, 2024 [February 4th, 2024]
- Why Some Folks Get COVID, and Others Never Do - HealthDay - February 4th, 2024 [February 4th, 2024]
- From plant genetics to fresh produce to be showcased in Berlin - FreshPlaza.com - February 4th, 2024 [February 4th, 2024]
- Adolescent Stress Alters Brain Genes, Affecting Adult Behavior - Neuroscience News - February 4th, 2024 [February 4th, 2024]
- Significance of genetic mutations in toxic tort cases - Massachusetts Lawyers Weekly - February 4th, 2024 [February 4th, 2024]
- New genetic test in England aims to make blood transfusions safer - Sickle Cell Disease News - February 4th, 2024 [February 4th, 2024]
- Unlocking tree genetic diversity: advanced hyperspectral phenotyping for enhanced Scots pine selection - EurekAlert - January 19th, 2024 [January 19th, 2024]
- The Role of Genetics in Cancer Care Continues to Expand - OncLive - January 19th, 2024 [January 19th, 2024]
- Family faces multiple diagnoses for genetic condition NF1 - Sanford Health News - January 19th, 2024 [January 19th, 2024]
- Unique gene variants tied to glaucoma found in Black patients - Livescience.com - January 19th, 2024 [January 19th, 2024]
- Myriad Genetics to Acquire Precise Tumor, Precise Liquid and Laboratory from Intermountain Precision Genomics - GlobeNewswire - January 19th, 2024 [January 19th, 2024]
- Reflections on the Idea of Social and Behavioral Genetics - The Hastings Center - January 19th, 2024 [January 19th, 2024]
- Building trust and saving lives: A community approach to genetic education - Medical University of South Carolina - January 19th, 2024 [January 19th, 2024]
- SOPHiA GENETICS and Karkinos Healthcare Forge Strategic Partnership to Advance Cancer Research in India India ... - PR Newswire - January 19th, 2024 [January 19th, 2024]
- 2024 Brevant Brand Corn Class Offers New Genetics and Traits - CropLife - January 19th, 2024 [January 19th, 2024]
- Genetics Reveal Poor Oral Health in Mesolithic Era - Mirage News - January 19th, 2024 [January 19th, 2024]
- Nova Siri Genetics strengthens its presence in Huelva, growing by 34% - FreshPlaza.com - January 19th, 2024 [January 19th, 2024]
- Controversial New Research Find That Bisexuals Are a Bunch of Rascals - Futurism - January 8th, 2024 [January 8th, 2024]
- Mayo Clinic Q&A: Weight loss and genetics - Chicago Tribune - January 8th, 2024 [January 8th, 2024]
- Nutrigene Launches Personalised Development Program to Intersect Genetics and Learning through DNA - JCN Newswire - January 8th, 2024 [January 8th, 2024]
- The DNA of privacy and the privacy of DNA - Federal Trade Commission News - January 8th, 2024 [January 8th, 2024]
- Development of a human genetics-guided priority score for 19365 genes and 399 drug indications - Nature.com - January 8th, 2024 [January 8th, 2024]
- Myriad Genetics, Inc.'s (NASDAQ:MYGN) Intrinsic Value Is Potentially 221% Above Its Share Price - Yahoo Finance - January 8th, 2024 [January 8th, 2024]
- Educational attainment of East Asians are linked to genetics - KBR - January 8th, 2024 [January 8th, 2024]
- MESuSiE enables scalable and powerful multi-ancestry fine-mapping of causal variants in genome-wide association ... - Nature.com - January 8th, 2024 [January 8th, 2024]