Characterization of EPO H131S as a key mutation site in the hypoxia-adaptive evolution of Gymnocypris dobula.

Erythropoietin (EPO) is a glycoprotein hormone involved in proerythropoiesis, antioxidation, and antiapoptosis. It also contributes to cellular immune function in high-altitude species, such as the schizothoracine fish Gymnocypris dobula. Six mutation sites previously identified in EPO from G. dobula (GD-EPO) were injected into zebrafish embryos, and their effects were compared with EPO from the low-altitude schizothoracine Schizothorax prenanti. The key mutation site in GD-EPO was identified as H131S. Under hypoxic conditions, the levels of superoxide dismutase and malondialdehyde were decreased, whereas that of nitric oxide was increased in zebrafish injected with GD-EPO compared with those injected with S. prenanti-EPO (SP-EPO). The results suggest that EPO in high-altitude schizothoracine species is both antioxidative and antiapoptotic, driven by the H131S mutation site. Thus, this enhanced the ability of this species to adapt to the high-altitude hypoxic environment. These results provide a basis for investigating further the hypoxia adaptation mechanisms of teleosts.