Genetic adaptations for life at high elevations found in residents of the Tibetan plateau likely originated around 30,000 years ago in peoples related to contemporary Sherpa.
Nature Communications, Anna Di Rienzo
This image shows the proportion of high-altitude ancestry (red) to low-altitude ancestry (green) in Sherpa, three groups of Tibetans, and lowland East Asians.
These genes were passed on to more recent migrants from lower elevations via population mixing, and then amplified by natural selection in the modern Tibetan gene pool, according to a new study by scientists from the University of Chicago and Case Western Reserve University, published in Nature Communications on Feb. 10.
The transfer of beneficial mutations between human populations and selective enrichment of these genes in descendent generations represents a novel mechanism for adaptation to new environments.
“The Tibetan genome appears to arise from a mixture of two ancestral gene pools,” said Anna Di Rienzo, PhD, professor of human genetics at the University of Chicago and corresponding author of the study. “One migrated early to high altitude and adapted to this environment. The other, which migrated more recently from low altitudes, acquired the advantageous alleles from the resident high-altitude population by interbreeding and forming what we refer to today as Tibetans.”
High elevations are challenging for humans because of low oxygen levels but Tibetans are well adapted to life above 13,000 feet. Due to physiological traits such as relatively low hemoglobin concentrations at altitude, Tibetans have lower risk of complications, such as thrombosis, compared to short-term visitors from low altitude. Unique to Tibetans are variants of the EGLN1 and EPAS1 genes, key genes in the oxygen homeostasis system at all altitudes. These variants were hypothesized to have evolved around 3,000 years ago, a date which conflicts with much older archaeological evidence of human settlement in Tibet.
To shed light on the evolutionary origins of these gene variants, Di Rienzo and her team, led by first author Choongwon Jeong, graduate student at the University of Chicago, obtained genome-wide data from 69 Nepalese Sherpa, an ethnic group related to Tibetans. These were analyzed together with the genomes of 96 unrelated individuals from high-altitude regions of the Tibetan plateau, worldwide genomes from HapMap3 and the Human Genome Diversity Panel, as well as data from Indian, Central Asian and two Siberian populations, through multiple statistical methods and sophisticated software.
The researchers found that, on a genomic level, modern Tibetans appear to descend from populations related to modern Sherpa and Han Chinese. Tibetans carry a roughly even mixture of two ancestral genomes: one a high-altitude component shared with Sherpa and the other a low-altitude component shared with lowlander East Asians. The low-altitude component is found at low to nonexistent frequencies in modern Sherpa, and the high-altitude component is uncommon in lowlanders. This strongly suggested that the ancestor populations of Tibetans interbred and exchanged genes, a process known as genetic admixture.
Tracing the history of these ancestor groups through genome analysis, the team identified a population size split between Sherpa and lowland East Asians around 20,000 to 40,000 years ago, a range consistent with proposed archaeological, mitochondria DNA and Y chromosome evidence for an initial colonization of the Tibetan plateau around 30,000 years ago.
“This is a good example of evolution as a tinkerer,” said Cynthia Beall, PhD, professor of anthropology at Case Western Reserve University and co-author on the study. “We see other examples of admixtures. Outside of Africa, most of us have Neanderthal genes—about 2 to 5 percent of our genome—and people today have some immune system genes from another ancient group called the Denisovans.”
The team also found that Tibetans shared specific high-altitude component traits with Sherpa, such as the EGLN1 and EPAS1 gene variants, despite the significant amount of genome contribution from lowland East Asians. Further analysis revealed these adaptations were disproportionally enhanced in frequency in Tibetans after admixture, strong evidence of natural selection at play. This stands in contrast to existing models that propose selection works through new advantageous mutations or on existing variants becoming beneficial in a new environment.
“The chromosomal locations that are so important for Tibetans to live at high elevations are locations that have an excess of genetic ancestry from their high-altitude ancestral gene pool,” Di Rienzo said. “This is a new tool we can use to identify advantageous alleles in Tibetans and other populations in the world that experienced this type of admixture and selection.”
In addition to the EPAS1 and EGLN1 genes, the researchers discovered two other genes with a strong proportion of high-altitude genetic ancestry, HYOU1 and HMBS. The former is known to be up-regulated in response to low oxygen levels and the latter plays an important role in the production of heme, a major component of hemoglobin.
“There is a strong possibility that these genes are adaptations to high altitude,” Di Rienzo adds. “They represent an example of how the ancestry-based approach used in this study will help make new discoveries about genetic adaptations.”
The study “Admixture-facilitated genetic adaptations to high altitude in Tibet,” was supported by the National Science Foundation. Additional authors include Gorka Alkorta-Aranburu, David B. Witonsky and Jonathan K. Pritchard from the University of Chicago, Buddha Basnyat from the Oxford University Clinical Research Unit at Patan Hospital in Nepal and Maniraj Neupane from the Mountain Medicine Society of Nepal.
The University of Chicago Medicine and Biological Sciences is one of the nation's leading academic medical institutions. It comprises the Pritzker School of Medicine, a top 10 medical school in the nation; the University of Chicago Biomedical Sciences Division; and the University of Chicago Medical Center, which recently opened the Center for Care and Discovery, a $700 million specialty medical facility. Twelve Nobel Prize winners in physiology or medicine have been affiliated with the University of Chicago Medicine.
Case Western Reserve University is one of the country’s leading private research institutions. Located in Cleveland, we offer a unique combination of forward-thinking educational opportunities in an inspiring cultural setting. Our leading-edge faculty engage in teaching and research in a collaborative, hands-on environment. Our nationally recognized programs include arts and sciences, dental medicine, engineering, law, management, medicine, nursing and social work. About 4,200 undergraduate and 5,600 graduate students comprise our student body.
Kevin Jiang | Newswise
New mechanisms uncovered explaining frost tolerance in plants
26.09.2016 | Technische Universität München
Chains of nanogold – forged with atomic precision
23.09.2016 | Suomen Akatemia (Academy of Finland)
The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.
“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...
With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.
Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...
For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.
Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...
At AKL’16, the International Laser Technology Congress held in May this year, interest in the topic of process control was greater than expected. Appropriately, the event was also used to launch the Industry Working Group for Process Control in Laser Material Processing. The group provides a forum for representatives from industry and research to initiate pre-competitive projects and discuss issues such as standards, potential cost savings and feasibility.
In the age of industry 4.0, laser technology is firmly established within manufacturing. A wide variety of laser techniques – from USP ablation and additive...
Every three years, the plastics industry gathers at K, the international trade fair for plastics and rubber in Düsseldorf. The Fraunhofer Institute for Laser Technology ILT will also be attending again and presenting many innovative technologies, such as for joining plastics and metals using ultrashort pulse lasers. From October 19 to 26, you can find the Fraunhofer ILT at the joint Fraunhofer booth SC01 in Hall 7.
K is the world’s largest trade fair for the plastics and rubber industry. As in previous years, the organizers are expecting 3,000 exhibitors and more than...
23.09.2016 | Event News
20.09.2016 | Event News
16.09.2016 | Event News
26.09.2016 | Materials Sciences
26.09.2016 | Materials Sciences
26.09.2016 | Materials Sciences