Physicochemical evolution and molecular adaptation of the cetacean osmoregulation-related gene UT-A2 and implications for functional studies.

Physicochemical evolution and molecular adaptation of the cetacean osmoregulation-related gene UT-A2 and implications for functional studies.
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鲸目动物渗透压调节相关基因 UT-A2 的物理化学进化和分子适应及其对功能研究的影响。

DOI:
10.1038/srep08795
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发表时间:
2015-03-12
期刊:
影响因子:
4.6
通讯作者:
Wang D
Wang D
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wang J;Yu X;Hu B;Zheng J;Xiao W;Hao Y;Liu W;Wang D

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鲸类动物有一段神秘的重新入侵水生栖息地的进化历史。使这一过程成为可能的一个重要适应性是它们的自我平衡策略调整。在这里,我们研究了鲸目动物尿素转运蛋白UT-A2的理化演变和分子适应,它在尿液浓度和水稳态中起着重要作用。首先,我们从长江江豚中克隆了UT-A2基因,并利用MEGA、PAML、DataMonkey、TreeSAAP和Consurf等软件对现有数据集(包括白暨豚和齿鲸)进行了生物信息学分析。我们的研究结果表明,UT-A2蛋白显示类似于dvUT和UT-B的折叠,而一些变化发生在选择性过滤器的功能性So和Si区域。此外,鲸类UT-A2蛋白的几个区域经历了分子适应。我们认为,积极的不稳定选择可能有助于适应影响其生化和构象特征。尿素传导孔的选择性过滤器内的氨基酸残基的保守性可能是尿素传导所必需的,而传导孔的入口和出口周围的非保守氨基酸替换可能潜在地影响活性,这可能是未来诱变研究的感兴趣的靶位点。
Cetaceans have an enigmatic evolutionary history of re-invading aquatic habitats. One of their essential adaptabilities that has enabled this process is their homeostatic strategy adjustment. Here, we investigated the physicochemical evolution and molecular adaptation of the cetacean urea transporter UT-A2, which plays an important role in urine concentration and water homeostasis. First, we cloned UT-A2 from the freshwater Yangtze finless porpoise, after which bioinformatics analyses were conducted based on available datasets (including freshwater baiji and marine toothed and baleen whales) using MEGA, PAML, DataMonkey, TreeSAAP and Consurf. Our findings suggest that the UT-A2 protein shows folding similar to that of dvUT and UT-B, whereas some variations occurred in the functional So and Si regions of the selectivity filter. Additionally, several regions of the cetacean UT-A2 protein have experienced molecular adaptations. We suggest that positive-destabilizing selection could contribute to adaptations by influencing its biochemical and conformational character. The conservation of amino acid residues within the selectivity filter of the urea conduction pore is likely to be necessary for urea conduction, whereas the non-conserved amino acid replacements around the entrance and exit of the conduction pore could potentially affect the activity, which could be interesting target sites for future mutagenesis studies.
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