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Lin Zeng, He-Qun Liu, Xiao-Long Tu, Chang-Mian Ji, Xiao Gou, Ali Esmailizadeh, Sheng Wang, Ming-Shan Wang, Ming-Cheng Wang, Xiao-Long Li, Hadi Charati, Adeniyi C. Adeola, Rahamon Akinyele Moshood Adedokun, Olatunbosun Oladipo, Sunday Charles Olaogun, Oscar J. Sanke, Mangbon Godwin F., Sheila Cecily Ommeh, Bernard Agwanda, Jacqueline Kasiiti Lichoti, Jian-Lin Han, Hong-Kun Zheng, Chang-Fa Wang, Ya-Ping Zhang, Laurent A. F. Frantz, Dong-Dong Wu. Genomes reveal selective sweeps in kiang and donkey for high-altitude adaptation. Zoological Research, 2021, 42(4): 450-460. doi: 10.24272/j.issn.2095-8137.2021.095
Citation: Lin Zeng, He-Qun Liu, Xiao-Long Tu, Chang-Mian Ji, Xiao Gou, Ali Esmailizadeh, Sheng Wang, Ming-Shan Wang, Ming-Cheng Wang, Xiao-Long Li, Hadi Charati, Adeniyi C. Adeola, Rahamon Akinyele Moshood Adedokun, Olatunbosun Oladipo, Sunday Charles Olaogun, Oscar J. Sanke, Mangbon Godwin F., Sheila Cecily Ommeh, Bernard Agwanda, Jacqueline Kasiiti Lichoti, Jian-Lin Han, Hong-Kun Zheng, Chang-Fa Wang, Ya-Ping Zhang, Laurent A. F. Frantz, Dong-Dong Wu. Genomes reveal selective sweeps in kiang and donkey for high-altitude adaptation. Zoological Research, 2021, 42(4): 450-460. doi: 10.24272/j.issn.2095-8137.2021.095


doi: 10.24272/j.issn.2095-8137.2021.095

Genomes reveal selective sweeps in kiang and donkey for high-altitude adaptation

Funds: This work was supported by the National Natural Science Foundation of China (31621062), Strategic Priority Research Program of the Chinese Academy of Sciences (XDA2004010302), and Second Tibetan Plateau Scientific Expedition and Research (STEP) Program (2019QZKK05010703). D.D.W. was supported by the National Natural Science Foundation of China (91731304, 31822048), Strategic Priority Research Program of the Chinese Academy of Sciences (XDB13020600), Qinghai Department of Science and Technology Major Project, and State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University (2018KF001). Sampling of this work was also supported by the Animal Branch of the Germplasm Bank of Wild Species, Chinese Academy of Sciences (Large Research Infrastructure Funding)
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  • 摘要: 在过去的几百年里,生活在青藏高原的家驴已经适应了高海拔的环境。有趣的是,同属于马科的近缘物种藏野驴也居住在这一地区。以往的研究阐述了不同谱系中特定基因的适应性渐渗对青藏高原低氧环境适应有重要的作用。在这项研究中,我们对藏家驴和藏野驴是否通过相同或不同的生物途径适应高原环境,以及是否发生了适应性渐渗现象展开了研究。我们从头组装了一个藏野驴的基因组,结合5个藏野驴和93个家驴(包括24个藏家驴)的基因组重测序数据展开了分析研究。分析表明,藏野驴EPAS1基因存在强的选择性清除信号;然而,藏家驴的高原适应,则是另一与高原适应相关的基因EGLN1,参与它们适应高海拔环境。此外,针对基因流的分析,我们未发现藏野驴和藏家驴中与高原适应相关的基因流动。我们的研究结果表明,尽管家驴在青藏高原的进化时间较短,且存在一个已经适应高原低氧环境的近缘物种,但藏家驴并没有通过与藏野驴的适应性渐渗来获得对高原的适应性,藏野驴与藏家驴这两个物种通过不同的生物途径进化出了对高原的适应能力。
    #Authors contributed equally to this work
  • Figure  1.  Genome evolution in kiangs

    A: Distribution of structural variants compared with horse genome. Tracks (outside to inside) show chromosomes, a: indel density, b: insertion density, c: deletion density, d: translocation density, e: gene density, f: repeat density. Density of indels, insertions, deletions, and translocations, was calculated from a 1 Mb non-overlapping sliding window, and 500 kb non-overlapping sliding window for gene density and repeat density of the horse. B: Expression analysis of REGs based on human expression data. Analysis was performed as described previously (Li et al., 2013). Human gene expression data (Human U133A Gene Atlas) in 84 tissues or cells were downloaded from BioGPS (Wu et al., 2016) (http://biogps.org/#goto=welcome). Relative expression level of REGs in each tissue was calculated by mean expression value of REGs in tissue divided by average whole-genome expression value. Only top 10 tissues/cell lines are presented. Species tree of six mammals was used to detect positively selected genes in kiang lineage (as foreground lineage) by branch site model in PAML. C: McDonald-Kreitman (MK) test identified several genes related to immunity, DNA damage, energy metabolism, and angiogenesis under positive selection in kiang lineage.

    Figure  2.  Population genetics analysis of kiangs and domestic donkeys

    A: Geographical location of domestic donkeys with re-sequenced genomes. Blue through light green indicate low to high altitude. B: Population structure analysis by Admixture with K from 2 to 5. C, D: No genetic introgression between kiang and Tibetan donkey was revealed by D-statistic and TreeMix.

    Figure  3.  Hard selective sweep in EPAS1 in kiangs

    A: Composite-likelihood ratio (CLR) detected by SweeD and nucleotide diversity levels around EPAS1 gene in different populations, including kiang, Tibetan donkey, and plain donkey. Results indicate that this gene likely experienced a hard selective sweep in kiangs. B: Haplotype of nucleotide mutations in EPAS1 showing high level of divergence between kiangs and domestic donkeys. Pink, yellow, blue, and black indicate genotypes of Homozygous variant, Heterozygote, Homozygous reference, and No call, respectively. C: Partial EPAS1 amino acid sequences among different species.

    Figure  4.  Rare hard selective sweep in kiangs at genome-wide scale

    Normalized nucleotide diversity was calculated as nucleotide diversity level in kiang population divided by donkey-kiang divergence around fixed substitutions using a non-overlapping window size of 10 kb.

    Figure  5.  Evidence of high-altitude adaptation in Tibetan domestic donkeys

    A: By comparing the genomes of Tibetan donkey populations and others, the genic region exhibited significantly higher FST values than the intergenic region. Statistical significance was calculated by Mann-Whitney U test. B: Population differentiation was more pronounced in non-synonymous SNPs than other types of SNPs. Statistical significance was calculated by chi-square test. C: A pattern of excess genic SNPs with high FST values (>0.4) between Tibetan domestic donkeys and lowland donkeys was found when constraining analyses to SNPs presenting similar minor allele frequencies (MAF). Statistical significance was calculated by chi-square test. D: Landscape of FST, Pi (nucleotide diversity), and LSBL values corroborates strong positive selection on EGLN1 gene. –log10 transformed FDR P-values are presented.

    Figure  6.  Selective sweep analysis by SweeD in kiang, Tibetan donkey, and plain donkey populations (A) and rare high CLR regions overlapped in the three populations(B)

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