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35 site is crucial for the activity of the Gs signaling pathway. In addition, our mutagenesis studies indicated that the positive selection sites of GPR39 from different species had important effects on the constitutive activity of the receptor. Our results revealed the adaptive evolution of GPR39 in diverse directions, which led to differences in constitutive activity. To determine if the 3-dimensional (3D) eyeball shape is associated with the positions of the central retinal vascular trunk (CRVT) and the externally oblique border (EOB