Comparative genomics reveals contraction in cytosolic glutathione transferase genes in cetaceans: implications for oxidative stress adaptation

Abstract

Cetaceans, a highly specialized group of aquatic mammals, experience oxidative stress induced by reactive oxygen species (ROS) production associated with the apnea/reoxygenation. The glutathione transferases (GST) family possesses multiple functions in detoxification and antioxidant defenses. However, the molecular evolution of GST family in cetaceans is still poorly investigated. Here, we characterized the GST gene family across 21 mammalian genomes including cetaceans and terrestrial relatives. Overall, 7 GST classes were identified, showing GSTs are ubiquitous and conservative to all mammals. Some of GSTs are lineage-specific duplication and loss, in line with a birth-and-death evolutionary model. We detected positive selection sites that possibly influence GST structure and function, suggesting adaptive evolution of GSTs is important for defending mammals from various types of noxious environmental compounds. There is evidence for loss of alpha and mu GST class in cetacean lineages when compared to their terrestrial relatives, consisting with the lower GST activities observed in cetaceans. Notably, we find that retained GSTA1, GSTA4 and GSTM1 in cetaceans, indicating a vital role in against lipid peroxidation and superoxide. Besides, variation in gene number, enzyme activity and selection pressure of GSTs between marine mammals suggests there is a divergent evolution of GSTs in aquatic species that might be associated to diving ability and oxidative status with different habitats. Summarily, our findings demonstrate that the GST family in cetaceans has been subject to evolutionary dynamics as response for their adaptations to oxidative stress, and highlighted the differential selection associated with different life history traits among mammals.