title: Physicochemical evolution and molecular adaptation of the cetacean osmoregulation-related gene UT-A2 and implications for functional studies.
abstract: 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.
authors.affiliation: 1] Key Laboratory of Aquatic Biodiversity and Conservation of the Chinese Academy of Sciences; Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei 430072, China [2] Marine Biology Institute, Shantou University, Shantou, Guangdong 515063, China.
authors.forename: Jingzhen
authors.initials: J
authors.lastname: Wang
authors.affiliation: 1] Key Laboratory of Aquatic Biodiversity and Conservation of the Chinese Academy of Sciences; Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei 430072, China [2] University of Chinese Academy of Sciences, Beijing 100039, China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Yu
authors.affiliation: Key Laboratory of Aquatic Biodiversity and Conservation of the Chinese Academy of Sciences; Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei 430072, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.affiliation: Key Laboratory of Aquatic Biodiversity and Conservation of the Chinese Academy of Sciences; Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei 430072, China.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Aquatic Biodiversity and Conservation of the Chinese Academy of Sciences; Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei 430072, China.
authors.forename: Wuhan
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Aquatic Biodiversity and Conservation of the Chinese Academy of Sciences; Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei 430072, China.
authors.forename: Yujiang
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Marine Biology Institute, Shantou University, Shantou, Guangdong 515063, China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Liu
authors.affiliation: Key Laboratory of Aquatic Biodiversity and Conservation of the Chinese Academy of Sciences; Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei 430072, China.
authors.forename: Ding
authors.initials: D
authors.lastname: Wang
mesh_terms: D000220:Adaptation, Biological; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D005075:Biological Evolution; D002591:Cetacea / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D008024:Ligands; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008958:Models, Molecular; D064587:Osmoregulation; D010802:Phylogeny; D011485:Protein Binding; D011487:Protein Conformation; D012333:RNA, Messenger / Q000235:genetics; D012641:Selection, Genetic; D000096982:Urea Transporters
chemical_list: D008024:Ligands; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D000096982:Urea Transporters