image: (A) The genetic structure of the population based on population SNPs. (B) The epigenetic structure of the population based on ethnic-specific DNA methylation sites. (C) The distribution curve of correlation values estimated between overall genetic distances and CpG methylation Manhattan distances of CpGs sorted with the values of Pst, the parameter to estimate phenotypic differentiation between populations. (D-E) The correlation curves based on the between-ethnic (D) or within-ethnic (E) comparison of genetic distances with CpG methylation Manhattan distances. view more
Credit: ©Science China Press
Recently, a paper entitled “Genome-wide DNA methylation landscape of four Chinese populations and epigenetic variation linked to Tibetan high-altitude adaptation” was published online in the journal SCIENCE CHINA Life Sciences. This study is led by Prof. Wen Wang (Northwestern Polytechnical University), Prof. Shuhua Xu (Fudan University), Prof. Zhengsheng Sun (Chinese Academy of Sciences), and associate Prof. Peng Tian (Northwest A&F University). Using the recently developed double strand bisulfite sequencing (DSBS) in Sun lab, this study revealed both genetic and DNA methylation variation in four Chinese ethnic groups, and investigated the potential difference and association of the two mechanisms in the population. Based on the comparison of Tibetan with other lowland individuals, they proposed potential function of epigenetic regulation in Tibetans’ adaptation to Qinghai-Tibet Plateau.
DNA methylation is one of the most important epigenetic marks in eukaryotic genome, and play important role in multiple cellular processes. Ongoing researches have showed the variation of DNA methylation among different human populations, and associated with both genetic and environmental factors. China is the most populous country in the world, which is consisted of 56 recognized ethnic groups. Geographical distribution and habitat differences are obvious among some ethnic populations. The most typical example is Tibetans’ adaptation to Qinghai-Tibet Plateau, which is low in oxygen while high in UV radiation. However, until the publication of this work, few study has analyzed the variation of DNA methylation among different ethnic groups in China, not to say the role of epigenetic regulation in Tibetans’ adaptation to high-altitude.
In this work, the authors collected blood samples from 32 participants that came from four Chinese ethnic groups including Chinese Han, Tibetan, Mongolian, and Zhuang. They carried out DSBS, the recently developed high-throughput sequencing technology that could accurately identify both single-nucleotide variants and DNA methylation simultaneously at a single-base resolution by using one dataset. The results of this study suggest that DNA methylation-based epigenetic structure is largely different with the genetic structure that could clearly distinguish the four ethnic groups (Figure 1A). Only a small part of the DNA methylation sites shows ethnic difference and could separate the four groups (Figure 1B). Surprisingly, they found non-ethnic-specific DNA methylation variations correlated more significantly to the global genetic divergence than these ethnic-specific DNA methylation after excluding the influence of within-ethnic and between-ethnic difference (Figure 1C-E), suggesting ethnic-specific DNA methylation variations were determined more by environmental factors other than genetic diversifications. Interestingly, they revealed that DNA methylation differences between Tibetan and other lowland individuals were enriched around high-altitude adaptation related genes including EPAS1 and EGLN1 (Figure 2), that were critical selection signals in Tibetans’ adaptation to highland, suggesting DNA methylation alteration plays an important role in high-altitude adaptation. Besides, they also discussed the accuracy of Nanopore sequencing in human epigenomic study, and explored the reliability and feasibility of this new technology at DNA methylation identification as compared to DSBS. This work not only provide the first batch of epigenetic comparison map for some important Chinese populations and the first evidence of the association of epigenetic changes with Tibetans’ high-altitude adaptation.
See the article:
Lin, Z., Lu, Y., Yu, G., Teng, H., Wang, B., Yang, Y., Li, Q., Sun, Z., Xu, S., Wang, W., et al. (2023). Genome-wide DNA methylation landscape of four Chinese populations and epigenetic variation linked to Tibetan high-altitude adaptation. Sci China Life Sci 66, https://doi.org/10.1007/s11427-022-2284-8
Journal
Science China Life Sciences