鲸类低氧耐受的分子机制初探:基于HIF1α和TSC1基因的生物信息学分析
更新日期:2021-07-06     浏览次数:161
核心提示:摘要鲸类(Cetacea)具有超强潜水能力,长时间潜水造成的体内低氧是其适应完全水生生活面临的挑战之一。为了克服体内低氧环境,鲸类产生了一系列低氧耐受

摘要 鲸类(Cetacea)具有超强潜水能力,长时间潜水造成的体内低氧是其适应完全水生生活面临的挑战之一。为了克服体内低氧环境,鲸类产生了一系列低氧耐受相关的解剖和生理等方面的适应特征,然而这一适应的分子机制仍不清楚。本研究选择在细胞感知和适应内环境氧分压变化的过程中发挥重要作用的低氧诱导因子(Hypoxia-inducible factor 1α,HIF1α)和低氧环境下抑制能量代谢的结节性复合物1(Tuberous sclerosis complex 1,TSC1)基因为候选基因,选择压力检测发现鲸类TSC1基因的6个正选择位点至少被两种最大似然法(Maximum Likelihood, ML)检测到,且通过与陆生哺乳动物同源序列比较分析,鲸类鉴定出7个特异的氨基酸突变。这些正选择和特异突变位点有30.77%(4/13)发生了激进氨基酸性质改变,且正选择位点位于重要结构域附近。正选择信号主要集中在鲸类内部各支系中,提示鲸类为了适应低氧环境,这两个基因可能发生了功能改变,以保护细胞免受低氧损伤。我们在低氧耐受不同类群间共检测到66个平行/趋同进化位点,为低氧耐受不同类群的趋同的低氧适应提供了分子证据。 Cetaceans are distinguished by their excellent diving ability.However, hypoxia is recognized as one of the biggest challenges for prolonged diving in cetaceans.Although cetaceans have evolved a series of anatomical and physiological traits related to hypoxic tolerance, the molecular mechanism of these adaptations are still unclear.In this study, we investigated two genes: hypoxia-inducible factor 1α(HIF1α)involved in cell sensing and adaptation to changes of oxygen partial pressure and tuberous sclerosis complex 1(TSC1)related to inhibition of energy metabolism in hypoxic environment.Our results revealed six positively selected sites of TSC1 gene in cetaceans that were detected by at least two ML methods.Moreover, compared with the homologous sequences of terrestrial mammals, seven specific amino acid mutations were identified in cetaceans.Additionally, 30.77% of these positively selected sites and specific mutation sites possessed radical amino acid changes.These positively selected sites were located in or closed to functional domains.Notably, signals of positive selection for HIF1α and TSC1 were mainly concentrated in cetacean lineages, suggesting that these two genes might have experienced functional changes to protect cells from hypoxia damage during adapting to aquatic environment.Interestingly, 66 parallel or convergent amino acid changes were detected among different hypoxic-tolerant species, which provides molecular evidence for the convergent hypoxic adaptation in mammals.
作者 刘瑞 曹阳 刘兴 田然 徐士霞 LIU Rui;CAO Yang;LIU Xing;TIAN Ran;XU Shixia(Jiangsu Key Laboratory for Biodiversity and Biotechnology,College of Life Sciences,Nanjing Normal University,Nanjing 210023,China)
出处 《兽类学报》 CAS CSCD 北大核心 2021年第3期296-309,共14页 Acta Theriologica Sinica
基金 国家自然科学基金项目(31772448)。
关键词 鲸类 低氧耐受 HIF1α基因 TSC1基因 Cetacea Hypoxia tolerance HIF1αgene TSC1 gene