Scientists constructed a map of adaptive genetic variation at the tibetan genome-wide level

The Xu Shuhua team of the Chinese Academy of Sciences-Map Institute of Computational Biology, through the research and analysis of deep genome sequencing data and Tibetan esopque data, constructed an adaptive genetic variation map of the whole genome level of the Tibetan population, and systematically presented the functional variation related to adaptive evolution in the Tibetan population genome for the first time. The findings were published online in the National Science Review.
After nearly ten years of intensive research at home and abroad, people have some preliminary understanding of the genetic basis of the adaptation of the Tibetan plateau, of which EPAS1 is currently widely regarded as the key gene of tibetan adaptation to the plateau, especially because of the discovery of epaS1 in other plateau species of adaptive evolution signs, so much attention has been paid. However, it has not been possible to determine the functional variation of EPAS1 gene with the Tibetan plateau, which leaves an unresolt problem for understanding the adaptive evolutionary mechanism of human beings on the Qinghai-Tibet Plateau.
To this end, Xu Shuhua team, in cooperation with researchers from
Kunming Animal Research Institute, Wenzhou Medical University, Fudan University, Tibet National University and other institutions, systematically combed the plateau adaptive variation of the Tibetan population at the whole genome level, made full use of the advantages of deep genome sequencing data, and constructed an adaptive genetic variation map on the whole genome scale of the Tibetan population. Key genetic variations with relatively clear functions, including 63 misalactant mutations, 7 inactive mutations, 1298 evolutionary conservative variants, and 509 gene expression quantitative variations, are not necessarily directly related to plateau adaptation in the Tibetan population, but most are closely related to the adaptive evolution of the Tibetan population.
plateau adaptation involves a complex set of complexities -- genes that may be more complex than some of the complex diseases studied in medicine. The team further developed a new statistical (FIS) weighted ranking of the relative importance of identified adaptive genetic variants, and found that the first place was not the usual EPAS1, but a trans-membrane protein coding gene TMEM247 located downstream of EPAS1;
"Our newly discovered key mutation in the TMEM247 gene (rs116983452) leads to a significant differentiation between high-frequency alanine (Ala) (wild type) in plain populations and proline (Val) (mutation type) unique to tibetan plateau populations, 94% of whom carry mutants, while the frequency in other modern population groups in the world is very low or completely missing, which is by far the highest frequency of mutations found in the genome of the Tibetan plateau population. Xu Shuhua, a researcher, told China Science Daily.
interestingly, an ancient human genome about 50,000 years old found in the Danisova cave in Siberia also carries this mutation and is pure. By calculating, the researchers concluded that the sequence of adaptive variations carrying TMEM247-rs116983452 in the Tibetan population dates back about 60,000 years, meaning that this Tibetan-specific high-frequency mutation may have inherited an ancestor of ancient human ancestry that entered the plateau in the early days and has been passed down to the present day.
fact, the process of human conquest of the Qinghai-Tibet Plateau has a long and tortuous history. Previous studies by Xu Shuhua's team have shown that the genetic origins of the People of the Qinghai-Tibet Plateau can be traced back to the late 40,000-60,000 years ago in the Middle and Late Stone Age, and extensive gene exchanges occurred among the human groups that entered the Qinghai-Tibet Plateau in the early years, and further genetic exchanges occurred with the ethnic groups that entered the Qinghai-Tibet Plateau in the later period. In this process, some of the ancient human gene fragments that helped human beings adapt to the highland environment were preserved, because of the natural selection of the extreme environment of the plateau, in today's plateau population accumulated to a higher frequency. TMEM247-rs116983452-T is a typical example.
analysis shows that the frequency of TMEM247-rs116983452-T is significantly positively related to the altitude of the population's place of residence, suggesting that there may be a close relationship with human adaptation in the Qinghai-Tibet Plateau. Further combining gene expression with a number of physiological, bio-ideotical ideotypes and physical anthropological characteristics, a systematic assessment of the adaptive genetic variation of the Tibetan population in the plateau was carried out, and it was found that TMEM247-rs116983452-T was closely related to the expression levels of TMEM247 and EPAS1, and may have important regulation on the adaptability of the plateau such as hemoglobin and erythrocyte levels in the low oxygen environment of the Tibetan population. Through statistical model analysis, the researchers found that TMEM247-rs116983452 explained the adaptive esoteric esotericity of the Tibetan plateau higher than the variation site of EPAS1, but there may be some interaction between the two, reflecting the complexity of plateau adaptation and the multi-gene interaction effect.
Xu Shuhua said the genome adaptive variation map provided by the study set the goal for further comprehensive and in-depth study of the genetic basis and molecular mechanisms of Tibetan adaptation to the plateau, and opened up new horizons for solving the mystery of the evolution of human conquest of the extreme environment of the plateau.
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