The adaptation of Tibetan people living in the plateau to the extremehypoxic environment is a typical example of human adaptive evolution. Previousgenetic analysis of Tibetan plateau adaptation has mainly focused on studies ofSingle Nucleotide Variants (SNVs) based on the second generation short-readlong sequencing data, and found two key genes associated with Tibetan plateauadaptation, EPAS1 and EGLN1, which explain the adaptation phenotype of lowerhemoglobin concentration in Tibetan population. However, in addition tohemoglobin concentration, other characteristics of Tibetan plateau adaptation(such as higher ventilation, lower pulmonary artery pressure, etc.) cannot beexplained by SNVs.

To systematically parse the entire genome of the Tibetan population, theresearchers assembled a high-quality Tibetan reference genome (Everest 1, ZF1)from scratch, using third-generation long read long sequence technology and avariety of assistive assembly techniques. The genome is the first high-qualityreference genome of a Tibetan population assembled from scratch with longfragment sequences, with better sequence continuity and integrity than theexisting human reference genome.

Using the genome, the researchers identified 17,900 SVs that occur inZF1, of which 6,505 are different from the SVs of the other two east Asians(HX1 and AK1). Functional enrichment analysis revealed that the functions of thesezf1-specific SVs related genes were significantly enriched in an importanthypoxic pathway - GTPase activity regulation pathway. By further populationanalysis, the researchers found a 163bp deletion in the intron of the MKL1gene, which showed a significant frequency difference between the Tibetan andhan populations and was significantly associated with lower pulmonary arterial pressurein the Tibetan population.

In addition, the researchers systematically evaluated the Tibetan genomefor fragments shared with ancient humans (neanderthals and denisovans) andfound that ZF1 had a higher proportion of shared fragments (1.32 to 1.53 percent)than the genomes of other east Asian individuals. A typical example is a 662bpinsertion on the intron of SCUBE2 gene, which was found to be rich in Tibetanand significantly correlated with lung function.

Source: http://xz.chinadaily.com.cn

Time: 2019.10.30