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.

Vertebral bone microarchitecture and osteocyte characteristics of three toothed whale species with varying diving behaviour

“…It has been reported in calcium-deprived conditions, such as vitamin D deficiency or lactation 35 , 36 . Cetaceans regulate their water metabolism via the uptake of liquids from food, seawater and their body fat 37 , 38 . Therefore, electrolyte regulation is fully adapted to the ingestion of salt water, which is calcium rich, and imbalanced calcium levels likely do not occur in whales.…”

Selection on different genes with equivalent functions: the convergence story told by Hox genes along the evolution of aquatic mammalian lineages

“…But only recently, the molecular mechanisms underlying such dramatic and convergent morphological changes during evolution of these three mammalian lineages began to be unraveled (e.g. [ 6 – 13 ]).…”

High‐quality whole‐genome sequence of an abundant Holarctic odontocete, the harbour porpoise (Phocoena phocoena)

“…With this in mind, we have located key genes (Table ) that may be under selection or underlie specific adaptive traits, both across cetaceans and in specific lineages (Chikina, Robinson, & Clark, ; McGowen, Gatesy, & Wildman, ; Yim et al., ). This includes genes with functions associated with low‐salinity and other cetacean‐specific traits, such as osmoregulation, reduction in smell, and taste receptors (Kishida et al., ; São Pedro et al., ; Wang et al., ). Among these, we found several genes from families linked to osmoregulation (e.g., AQP2, AGT, SLC14A2; São Pedro et al., ; Xu et al., ), which have been inferred to be under positive selection in cetaceans.…”

“…With this in mind, we have located key genes (Table 5) that may be under selection or underlie specific adaptive traits, both across cetaceans and in specific lineages (Chikina, Robinson, & Clark, 2016;McGowen, Gatesy, & Wildman, 2014;Yim et al, 2014). This includes genes with functions associated with low-salinity and other cetacean-specific traits, such as osmoregulation, reduction in smell, and taste receptors (Kishida et al, 2015;São Pedro et al, 2015;Wang et al, 2015).…”