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

Jingzhen Wang,Wuhan Xiao,Yujiang Hao,Xueying Yu,Ding Wang,Bo Hu,Jinsong Zheng,Wenhua Liu

doi:10.1038/srep08795

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.

Highlights

Physicochemical Evolution and Molecular Adaptation of the Cetacean Osmoregulation-related Gene UT-A2 and Implications for Functional Studies
1) Have the UT-A2 genes evolved adaptively during cladogenesis, when cetaceans transitioned from land to the marine environments? And 2) are there any molecular adaptations in UT-A2 between the extant seawater and freshwater cetaceans that could provide an adaptive advantage in facing different osmoregulatory challenges?
We looked for evidence of adaptive molecular evolution of the osmoregulation-correlated gene UT-A2 in the cetacean lineage, relative to their terrestrial counterparts

Summary

Introduction

Physicochemical Evolution and Molecular Adaptation of the Cetacean Osmoregulation-related Gene UT-A2 and Implications for Functional Studies. Cetaceans face the challenge of osmotic diuresis; if urea in the collecting ducts is highly concentrated and UT regulation is lacking, it will draw water from the kidney interstitium and lead to undesirably increased water excretion This means that UT is essential to cetacean osmoregulation. Our recent studies showed that the Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis, YFP), which resides in hypo-osmotic freshwater (Yangtze river) likely excretes relatively less concentrated urine (934 mOsm/ kg) compared to its marine counterparts that include Bohai finless porpoises (Neophocaena asiaeorientalis sunameri)[25]. These observations regarding urine concentration lead to two questions. These observations regarding urine concentration lead to two questions. 1) Have the UT-A2 genes (which are correlated with urine concentration abilities in mammals) evolved adaptively during cladogenesis, when cetaceans transitioned from land to the marine environments? And 2) are there any molecular adaptations in UT-A2 between the extant seawater and freshwater cetaceans that could provide an adaptive advantage in facing different osmoregulatory challenges?

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Results

Conclusion