4.8 Article

Long read genome assemblies complemented by single cell RNA-sequencing reveal genetic and cellular mechanisms underlying the adaptive evolution of yak

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NATURE COMMUNICATIONS
卷 13, 期 1, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41467-022-32164-9

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资金

  1. Second Tibetan Plateau Scientific Expedition and Research (STEP) Program [2019QZKK0302]
  2. Strategic Priority Research Program of Chinese Academy of Sciences [XDA2005010406]
  3. National Key R&D Program of China [2021YFD1200405]
  4. National Natural Science Foundation of China [31972574]
  5. Qinghai Science and Technology Major Program Sanjiangyuan National Park Animal Genome Project
  6. Natural Science Program [2020-ZJ-902]
  7. CAS 100 Talents program
  8. Qinghai 1000 Talents program

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In this study, we assembled two chromosome-level genomes for wild and domestic yaks, and identified structural variants (SVs) and differentially expressed genes related to high-altitude adaptation. Additionally, the construction of a single-cell gene expression atlas revealed a yak-specific endothelial cell subtype. These findings provide new insights into the genetic and cellular basis of yak adaptation to high-altitude environments and have important implications for understanding responses to hypoxia in large mammals and humans.
Wild yak (Bos mutus) and domestic yak (Bos grunniens) are adapted to high altitude environment and have ecological, economic, and cultural significances on the Qinghai-Tibetan Plateau (QTP). Currently, the genetic and cellular bases underlying adaptations of yak to extreme conditions remains elusive. In the present study, we assembled two chromosome-level genomes, one each for wild yak and domestic yak, and screened structural variants (SVs) through the long-read data of yak and taurine cattle. The results revealed that 6733 genes contained high-FST SVs. 127 genes carrying special type of SVs were differentially expressed in lungs of the taurine cattle and yak. We then constructed the first single-cell gene expression atlas of yak and taurine cattle lung tissues and identified a yak-specific endothelial cell subtype. By integrating SVs and single-cell transcriptome data, we revealed that the endothelial cells expressed the highest proportion of marker genes carrying high-FST SVs in taurine cattle lungs. Furthermore, we identified pathways which were related to the medial thickness and formation of elastic fibers in yak lungs. These findings provide new insights into the high-altitude adaptation of yak and have important implications for understanding the physiological and pathological responses of large mammals and humans to hypoxia.

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