An Zhifang, Chen Xiaoqi, Li Jimei
State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, China.
Department of Obstetrics and Gynaecology, Affiliated Hospital of Qinghai University, Xining, China.
Front Genet. 2022 Jun 8;13:865301. doi: 10.3389/fgene.2022.865301. eCollection 2022.
The plateau zokor () 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 (pO) 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) pO conditions. Our results showed that, (1) the sequences of the apoptosis-related genes in plateau zokor were highly similar to those of , followed by ; (2). Pidd, Puma, Igfbp3, and Apaf1 of plateau zokor were found to have five, one, two, and five convergent sites in functional domains with , respectively. Lastly (3), under low pO, the expression of and was downregulated in the lung of plateau zokors. In turn, and were upregulated in the liver and lung, and was upregulated in the skeletal muscle of plateau zokor under low pO. In Sprague-Dawley rats, low pO downregulated and expression in the liver and downregulated and in the lung and skeletal muscle separately. In contrast, low pO upregulated expression in the liver and skeletal muscle of Sprague-Dawley rats. Overall, the expression patterns of , , and 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, , , , and 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.
高原鼢鼠()是青藏高原的本土物种,其一生都生活在缺氧的封闭洞穴中。本研究旨在评估高原鼢鼠和Sprague-Dawley大鼠中凋亡相关基因的序列特征以及对不同氧分压(pO)的反应。评估了含死亡结构域的p53诱导蛋白(Pidd)、p53上调凋亡调节因子(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)的序列的同源性和趋同进化位点,并在14.13(3300米)和16.12千帕(2260米)pO条件下评估了它们在不同组织中的mRNA水平。我们的结果表明,(1)高原鼢鼠中凋亡相关基因的序列与的高度相似,其次是;(2)发现高原鼢鼠的Pidd、Puma、Igfbp3和Apaf1在功能结构域中分别与有五个、一个、两个和五个趋同位点。最后(3),在低pO条件下,高原鼢鼠肺中的和表达下调。反过来,在低pO条件下,高原鼢鼠肝脏和肺中的和上调,骨骼肌中的上调。在Sprague-Dawley大鼠中,低pO分别下调了肝脏中的和表达,下调了肺和骨骼肌中的和表达。相反,低pO上调了Sprague-Dawley大鼠肝脏和骨骼肌中的表达。总体而言,与Sprague-Dawley大鼠相比,高原鼢鼠肝脏、肺和骨骼肌中的、和表达模式分别呈现相反的模式。总之,为了长期适应缺氧环境,高原鼢鼠的、、、和经历了趋同进化,我们认为这可能导致它们在低氧分压下水平上调以诱导凋亡,从而抑制高原鼢鼠缺氧环境下的肿瘤发生。