People who visit the Andes Mountains in South America may experience the physical effects of lower oxygen levels at higher altitudes. However, some people living there have evolved over hundreds of generations to tolerate these low-oxygen conditions. Credit: Elysia Cook McDermott
Humans are still evolving, and Tatum Simonson, Ph.D., founder and co-director of the Center for Physiological Genomics of Low Oxygen at the University of California School of Medicine, plans to use evolution to improve health care for all.
His latest research, published on February 9, 2024 in Scientists progress, reveals that a genetic variant in some Andean peoples is associated with a reduction in red blood cell counts at high altitudes, allowing them to live safely in high mountains in low-oxygen conditions. Simonson’s lab at UC San Diego is applying these findings to understand whether there may be a genetic component to why some people with sleep apnea or lung diseases such as chronic obstructive pulmonary disease (COPD) come out better than others.
Simonson explained: “Some people with COPD breathe heavily and maintain higher oxygen saturation. Other people with the same condition don’t breathe as much and their oxygen saturation is low. The researchers suspect that 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 altitudes. .
Our cells need oxygen to survive. When there isn’t enough of it in the environment, our bodies produce extra red blood cells that carry oxygen throughout the body. However, excess red blood cells create a dangerous condition called excessive erythrocytosis (EE), which makes the blood viscous, which could lead to stroke or heart failure.
His previous research showed that many Tibetans living in the mountains and exposed to low oxygen situations are born with innate mechanisms that protect them from poor outcomes at high altitude, including overproduction of red blood cells. This is partly due to changes in the regulation of EPAS1 gene, which lowers hemoglobin concentrations by regulating the pathway that responds to changes in 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 ago – a unique evolutionary history confined to this population.
For his 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 and Physiology at the University School of Medicine UC San Diego, zoomed in on the EPAS1 region of the genome. She and her team focused on a gene mutation present in some people living in the Andes but absent in all other human populations. By analyzing entire Andean genomes, they discovered a pattern around this variant suggesting that the genetic change, which alters a single amino acid in the protein product, occurred by chance, relatively recently (9,000 to 13 000 years) and spread very quickly. rapidly through hundreds of generations within the Andean population.
Similar to the Tibetans, the EPAS1 The gene is associated with a decrease in the number of red blood cells in Andeans who possess it. However, the researchers were surprised to find that the variant functions 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 of each cell.
UC San Diego researchers have discovered that a genetic variant in some Andean peoples is associated with a reduction in red blood cell counts at high altitudes, allowing them to live safely in high mountains in low-equivalent conditions. oxygen. The findings could help scientists improve precision medicine for sleep apnea and lung diseases, such as chronic obstructive pulmonary disease (COPD). Credit: Elysia Cook McDermott
“Tibetans have, in general, a lower average hemoglobin concentration, and their physiology manages low oxygen levels so as not to increase their red blood cells to excessively high levels. We now have the first signs that the Andeans also go this route, involving the same gene, but with a protein-coding change. Evolution worked in these two populations, on the same gene, but in different ways,” Simonson said.
This study illustrates a current approach to research that links genetic targets of natural selection to complex disease genes – understanding, for example, how natural genetic variation contributes to adaptive and maladaptive responses to a lack of oxygen, such as this study reveals.
In Simonson’s lab, that means determining which downstream target genes are activated in response to low oxygen, among other things. Simonson said: “This paper shows one gene associated with a particular phenotype, but we believe many different genes and components of oxygen transport are involved. This is only one piece of this puzzle and could provide researchers with information relevant to other populations.”
Simonson and his team work 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 when they are awake and asleep . They are cross-referencing their findings with publicly available databases to determine whether the discoveries they made among Andeans are also found among local Latinos who may share certain genetic variants with Andeans.
“In precision medicine, it is important to recognize variations in genetic background, especially in historically understudied populations,” Simonson said. “If we can find shared genetic factors in populations living in an extreme environment, this could help us understand aspects of health and disease in this group and in these groups more locally. In this way, this study aims to advance research and achieve personalized, comprehensive medical approaches in clinics here in San Diego.
More information:
Elijah S. Lawrence et al, EPAS1/HIF2A functional missense variant is associated with hematocrit in Andean highlanders, Scientists progress (2024). DOI: 10.1126/sciadv.adj5661
Provided by University of California – San Diego
Quote: Harnessing human evolution to advance precision medicine (February 10, 2024) retrieved February 10, 2024 from
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