Cetaceans are distinguished by their excellent diving ability. However, hypoxia is recognized as one of the biggest challenges for prolonged diving in cetaceans. Although cetaceans have evolved a series of anatomical and physiological traits related to hypoxic tolerance, the molecular mechanism of these adaptations are still unclear. In this study, we investigated two genes:hypoxia-inducible factor 1α (HIF1α) involved in cell sensing and adaptation to changes of oxygen partial pressure and tuberous sclerosis complex 1(TSC1) related to inhibition of energy metabolism in hypoxic environment. Our results revealed six positively selected sites of TSC1 gene in cetaceans that were detected by at least two ML methods. Moreover, compared with the homologous sequences of terrestrial mammals, seven specific amino acid mutations were identified in cetaceans. Additionally, 30.77% of these positively selected sites and specific mutation sites possessed radical amino acid changes. These positively selected sites were located in or closed to functional domains. Notably, signals of positive selection for HIF1α and TSC1 were mainly concentrated in cetacean lineages, suggesting that these two genes might have experienced functional changes to protect cells from hypoxia damage during adapting to aquatic environment. Interestingly, 66 parallel or convergent amino acid changes were detected among different hypoxic-tolerant species, which provides molecular evidence for the convergent hypoxic adaptation in mammals.
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