Genomic structural variation is associated with hypoxia adaptation in high-altitude zokors

Xuan An, Leyan Mao, Yinjia Wang, Qinqin Xu, Xi Liu, Shangzhe Zhang, Zhenglei Qiao, Bowen Li, Fang Li, Zhuoran Kuang, Na Wan, Xiaolong Liang, Qijiao Duan, Zhilong Feng, Xiaojie Yang, Sanyuan Liu, Eviatar Nevo, Jianquan Liu, Jay F Storz, Kexin Li

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Zokors, an Asiatic group of subterranean rodents, originated in lowlands and colonized high-elevational zones following the uplift of the Qinghai-Tibet plateau about 3.6 million years ago. Zokors live at high elevation in subterranean burrows and experience hypobaric hypoxia, including both hypoxia (low oxygen concentration) and hypercapnia (elevated partial pressure of CO2). Here we report a genomic analysis of six zokor species (genus Eospalax) with different elevational ranges to identify structural variants (deletions and inversions) that may have contributed to high-elevation adaptation. Based on an assembly of a chromosome-level genome of the high-elevation species, Eospalax baileyi, we identified 18 large inversions that distinguished this species from congeners native to lower elevations. Small-scale structural variants in the introns of EGLN1, HIF1A, HSF1 and SFTPD of E. baileyi were associated with the upregulated expression of those genes. A rearrangement on chromosome 1 was associated with altered chromatin accessibility, leading to modified gene expression profiles of key genes involved in the physiological response to hypoxia. Multigene families that underwent copy-number expansions in E. baileyi were enriched for autophagy, HIF1 signalling and immune response. E. baileyi show a significantly larger lung mass than those of other Eospalax species. These findings highlight the key role of structural variants underlying hypoxia adaptation of high-elevation species in Eospalax.

Original languageEnglish
Pages (from-to)339-351
Number of pages13
JournalNature Ecology and Evolution
Issue number2
Early online date9 Jan 2024
Publication statusPublished - 1 Feb 2024


  • Animals
  • Altitude
  • Phylogeny
  • Rodentia/genetics
  • Hypoxia/genetics
  • Genomic structural variation


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