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Abstract：
The plateau zokor (Myospalax baileyi) is a native species of the Qinghai-Tibet Plateau that spends its entire life underground in sealed burrows with hypoxic conditions. The present study aimed to assess the sequence characteristics of apoptosis-related genes and the response to different oxygen partial pressures (pO2) in plateau zokor and Sprague-Dawley rats. The sequences of the p53-induced protein with a death domain (Pidd), p53-upregulated modulator of apoptosis (Puma), insulin-like growth factor binding protein 3 (Igfbp3), and apoptosis protease-activating factor 1 (Apaf1) were evaluated concerning homology and convergent evolution sites, and their mRNA levels were evaluated in different tissues under 14.13 (3,300 m) and 16.12 kPa (2,260 m) pO2 conditions. Our results showed that, (1) the sequences of the apoptosis-related genes in plateau zokor were highly similar to those of Nannospalax galili, followed by Rattus norvegicus; (2). Pidd, Puma, Igfbp3, and Apaf1 of plateau zokor were found to have five, one, two, and five convergent sites in functional domains with N. galili, respectively. Lastly (3), under low pO2, the expression of Pidd and Puma was downregulated in the lung of plateau zokors. In turn, Igfbp3 and Apaf1 were upregulated in the liver and lung, and Puma was upregulated in the skeletal muscle of plateau zokor under low pO2. In Sprague-Dawley rats, low pO2 downregulated Puma and Apaf1 expression in the liver and downregulated Igfbp3 and Puma in the lung and skeletal muscle separately. In contrast, low pO2 upregulated Pidd expression in the liver and skeletal muscle of Sprague-Dawley rats. Overall, the expression patterns of Apaf1, Igfbp3, and Puma showed the opposite pattern in the liver, lung, and skeletal muscle, respectively, of plateau zokor as compared with Sprague-Dawley rats. In conclusion, for the long-time adaptation to hypoxic environments, Pidd, Puma, Igfbp3, and Apaf1 of plateau zokor underwent convergent evolution, which we believe may have led to upregulation of their levels under low oxygen partial pressures to induce apoptosis, so as to suppress tumorigenesis under hypoxic environments in plateau zokor.
摘要：
高原zokor（Myospalaxbaileyi）是青藏高原的一种本地物种，一生都在缺氧条件下的封闭洞穴中度过。本研究旨在评估高原zokor和Sprague-Dawley大鼠的凋亡相关基因的序列特征以及对不同氧分压（pO2）的反应。带有死亡结构域（Pidd）的p53诱导蛋白的序列，p53上调的细胞凋亡调节剂（Puma），胰岛素样生长因子结合蛋白3（Igfbp3），和凋亡蛋白酶激活因子1（Apaf1）进行了同源性和趋同进化位点的评估，并在14.13（3,300m）和16.12kPa（2,260m）pO2条件下评估了它们在不同组织中的mRNA水平。我们的研究结果表明,（1）高原zokor的凋亡相关基因序列与Nannospalaxgalili的高度相似，其次是褐家鼠；（2）。皮德,美洲狮,高原zokor的Igfbp3和Apaf1被发现有五个，一,两个,和功能域中的五个收敛位点，分别。最后（3），在低pO2下，Pidd和Puma在高原zokors肺中的表达下调。反过来,Igfbp3和Apaf1在肝脏和肺中上调，在低pO2下，高原zokor骨骼肌中Puma表达上调。在Sprague-Dawley老鼠身上,低pO2下调肝脏中Puma和Apaf1的表达，并分别下调肺和骨骼肌中的Igfbp3和Puma。相比之下,低pO2上调Sprague-Dawley大鼠肝脏和骨骼肌中Pidd的表达。总的来说,Apaf1，Igfbp3和Puma的表达模式在肝脏中显示出相反的模式，肺，和骨骼肌，分别,与Sprague-Dawley大鼠相比，高原zokor。总之,为了长期适应缺氧环境，皮德,美洲狮,高原zokor的Igfbp3和Apaf1经历了趋同进化，我们认为这可能导致在低氧分压下它们的水平上调以诱导细胞凋亡，从而抑制高原zokor低氧环境下的肿瘤发生。
