The role of the 3′ region of mammalian gonadotropin β subunit gene in the luteinizing hormone to chorionic gonadotropin evolution

CG beta subunits comprise a unique carboxyl-terminal peptide (CTP) that has multiple O-linked glycans and extends serum half-life of the protein. It has evolved by incorporating a previously untranslated region of the LH beta gene into the reading frame. Although CTP-like sequences are encrypted in the LH beta genes of several mammals, the CGO subunit developed only in primates and equids. To study this restriction in evolution, we examined whether the cryptic CTP decoded from the bovine LH beta gene (boCTP) possesses key characteristics of the human (h) CG beta-CTP. The boCTP does not impede several crucial aspects of hormone biosynthesis, but compared to the hCGB-CTP, the stretch lacks O-glycans and determinants for circulatory survival. O-glycan deficiency and the associated incapacity to extend serum half-life is a major drawback of the boCTP. This may explain why LH did not evolve into CG in ruminants and consequently alternative mechanisms evolved to delay luteolysis early in gestation. (c) 2013 Elsevier Ireland Ltd. All rights reserved.