Cetacean-specific GPR12 mutation is functionally associated with blubber thickening

To cope with thermal challenges of aquatic environments, marine mammals, including cetaceans, sirenians, and pinnipeds, independently evolved a substantially thickened subcutaneous blubber layer compared to terrestrial relatives. The blubber is a specialized adipose tissue layer under the skin of marine mammals and is vital for heat insulation, energy storage, buoyancy control and enhancement of locomotion. However, the molecular evolutionary mechanism underlying blubber thickening remains largely unexplored. An evolutionary analysis of the mammalian GPR12 gene was conducted to identify a cetacean-specific amino acid substitution that is absent in any other mammals. In vitro cellular experiments suggested that this amino acid substitution could reduce the expression of adipose triglyceride lipase (ATGL) and thereby decrease lipolytic activity. This study uncovered critical genetic signals which could influence lipolysis capacity in cetaceans and might have been the evolutionary mechanism underlying the blubber thickening in cetaceans during secondary aquatic adaptation.