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安志芳,魏琳娜,王志洁,李苏华,徐波,魏莲,魏登邦.2019.高原鼢鼠肺组织细胞凋亡相关 基因的进化分析及其在不同 海拔条件下的表达模式.动物学杂志,54(4):549-566.
高原鼢鼠肺组织细胞凋亡相关 基因的进化分析及其在不同 海拔条件下的表达模式
Evolution Analysis of Apoptotic Genes and Their Expression Patterns in Lung Tissues of Plateau Zokors (Myospalax baileyi) Inhabiting at Different Altitudes
投稿时间:2018-11-03  修订日期:2019-06-08
DOI:10.13859/j.cjz.201904012
中文关键词:  高原鼢鼠  细胞凋亡基因  进化分析  表达  低氧
英文关键词:Plateau zokor (Myospalax baileyi)  Apoptotic target genes  Evolution analysis  Expression  Hypoxia
基金项目:青海省自然科学基金项目(No. 2016-ZJ-901)
作者单位E-mail
安志芳 ① 青海大学省部共建三江源生态与高原农牧业国家重点实验室 西宁 810016② 青海大学医学院 西宁 810016 anzhifang90@126.com 
魏琳娜 ③青海大学农牧学院 西宁 810016 weilinna92@126.com 
王志洁 ① 青海大学省部共建三江源生态与高原农牧业国家重点实验室 西宁 810016② 青海大学医学院 西宁 810016 wzjob604@163.com 
李苏华 ① 青海大学省部共建三江源生态与高原农牧业国家重点实验室 西宁 810016② 青海大学医学院 西宁 810016 18509713631@163.com 
徐波 ① 青海大学省部共建三江源生态与高原农牧业国家重点实验室 西宁 810016③青海大学农牧学院 西宁 810016 18409789409@163.com 
魏莲 ③青海大学农牧学院 西宁 810016 weilian5318@126.com 
魏登邦 ① 青海大学省部共建三江源生态与高原农牧业国家重点实验室 西宁 810016② 青海大学医学院 西宁 810016 weidengbang@163.com 
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中文摘要:
      高原鼢鼠(Myospalax baileyi)是青藏高原特有的地下鼠,其地下洞道严重缺氧。一般来说,低氧会促进细胞凋亡。为了探讨高原鼢鼠适应低氧环境的分子机制,本文应用生物信息学方法对p53下游凋亡促进基因Pidd、Fas、Bax、Puma、Apaf-1、Scotin、Perp、Igfbp3和凋亡抑制基因Bcl-2的序列和编码的氨基酸序列进行了进化分析,并以SD大鼠(Rattus norvegicus)为对照,研究了这些基因在不同海拔环境条件下(3 300 m和2 260 m)的表达模式。结果表明:(1)高原鼢鼠细胞凋亡基因的序列与以色列鼹鼠(Nannospalax galili)同源性最高;预测的PIDD、PUMA、Apaf-1、IGFBP3和BCL-2编码蛋白结构域与以色列鼹鼠的存在明显的趋同进化位点;SIFT评估发现,高原鼢鼠和以色列鼹鼠与其他物种相比,p53、PIDD、PUMA、Apaf-1和IGFBP3氨基酸序列分别在78、853、157、320和285号位点的变异对其功能有显著影响;(2)在高海拔条件下(3 300 m),高原鼢鼠肺组织中凋亡促进基因Pidd、Bax、Puma和Apaf-1表达水平显著下降,凋亡抑制基因Bcl-2表达水平显著升高,而在SD大鼠中凋亡促进基因和凋亡抑制基因的表达水平均没有变化;高原鼢鼠中Bcl-2/Bax比值随海拔的升高显著上升,而在SD大鼠中没有变化。以上结果提示,高原鼢鼠p53结构变异可能导致其下游基因表达模式与SD大鼠不同,其中凋亡促进基因Pidd、Bax、Puma和Apaf-1表达水平下降,凋亡抑制基因Bcl-2表达水平上升,从而抑制了细胞在低氧条件下的凋亡;在长期低氧的作用下,高原鼢鼠p53下游基因产物PIDD、PUMA、Apaf-1和IGFBP3产生了影响其功能的变异位点,这可能改变了它们与发挥功能的复合物的结合力,从而抑制了细胞凋亡。因此,通过长期的低氧适应,高原鼢鼠肺组织中与细胞凋亡相关的基因产物结构发生变异,导致其基因表达水平发生变化,从而抑制细胞凋亡,这是高原鼢鼠适应地下低氧洞道生境的分子机制之一。
英文摘要:
      The plateau zokor (Myospalax baileyi) is a specialized subterranean rodent living on the Qinghai-Tibet Plateau, which is short of oxygen in burrows. In general, hypoxia can induce apoptosis. In order to shed lights into the molecular mechanism of the plateau zokor adaptation to the hypoxic environment, the sequences of Pidd, Fas, Bax, Puma, Apaf-1, Scotin, Perp, Igfbp3 and Bcl-2 were analyzed by MEGA 7.0, PAML4.8 program and Ancestor program. In addition, the expression levels of these genes were determined with real-time PCR in the lung tissues of zokors inhabiting at different altitudes (3 300 m and 2 260 m) and compared with the SD rats in this study. The sequences of the apoptotic target genes in plateau zokors were highly homologous those of Nannospalax galili (Table 2 and Table 3). PIDD (Fig. 2), PUMA (Fig. 3), Apaf-1 (Fig. 4), IGFBP3 (Fig. 5) and BCL-2 (Fig. 6) in plateau zokor and Nannospalax galili showed convergent sites in their functional domains. The SIFT test showed that, compared to other species, 78, 853, 157, 320 and 285 variation sites of plateau zokor and Nannospalax galili had effects on the function of p53, PIDD, PUMA, Apaf-1 and IGFBP3, respectively (Table 5). At the high altitude (3 300 m), the expression levels of proapoptotic genes Pidd, Bax and Puma were significantly decreased, while the expression level of antiapoptotic gene Bcl-2 was significantly increased; instead, the expression levels of proapoptotic and antiapoptotic genes showed no significant difference in SD rats. The expression levels of apoptotic genes in plateau zokor were higher than in the SD rats (Fig. 7, 8). At the high altitude (3 300 m), the ratio of Bcl-2/Bax expression was significantly increased in plateau zokor, whereas that of the SD rat was not (Fig. 9). The results above suggested that site variation of p53 in plateau zokor resulted in different expression patterns of p53 targeted apoptotic genes from those in SD rat: the expression levels of proapoptotic genes Pidd, Bax, Puma and Apaf-1 were decreased, while the expression level of antiapoptotic gene Bcl-2 was increased, so as to inhibit apoptosis under hypoxic environment. Under the long-term hypoxia conditions, the p53 targeted proteins PIDD, PUMA, Apaf-1 and IGFBP3 had significant variation sites, which might alter their ability to combine with their functional complexes and inhibit apoptosis. Therefore, over the long-term hypoxia adaptation, the apoptotic genes of plateau zokor underwent structural variation, leading to change in the expression levels of these genes, and thereby inhibited apoptosis, which is one of the molecular mechanisms of plateau zokor adaption to the hypoxic burrowing environment.
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