The role of the 3' region of mammalian gonadotropin β subunit gene in the luteinizing hormone to chorionic gonadotropin evolution.
CGβ 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 LHβ gene into the reading frame. Although CTP-like sequences are encrypted in the LHβ genes of several mammals, the CGβ subunit developed only in primates and equids. To study this restriction in evolution, we examined whether the cryptic CTP decoded from the bovine LHβ gene (boCTP) possesses key characteristics of the human (h) CGβ-CTP. The boCTP does not impede several crucial aspects of hormone biosynthesis, but compared to the hCGβ-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.
Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Reut
R
Gabay
Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Shelly
S
Rozen
Procognia (Israel) Ltd., Ashdod, Israel.
Albena
A
Samokovlisky
Procognia (Israel) Ltd., Ashdod, Israel.
Yehudit
Y
Amor
Procognia (Israel) Ltd., Ashdod, Israel.
Rakefet
R
Rosenfeld
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
Fortune
F
Kohen
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Abraham
A
Amsterdam
Endocrinology Unit, Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, Austria.
Peter
P
Berger
Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. Electronic address: dbm@bgu.ac.il.
David
D
Ben-Menahem
D024509:3' Flanking Region; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002417:Cattle; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D003412:Cricetulus; D019143:Evolution, Molecular; D005260:Female; D005786:Gene Expression Regulation; D006207:Half-Life; D006736:Horses; D006801:Humans; D007986:Luteinizing Hormone / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry* / Q000378:metabolism; D011247:Pregnancy; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051381:Rats
D018997:Chorionic Gonadotropin, beta Subunit, Human; D010455:Peptides; D011134:Polysaccharides; D021122:Protein Subunits; D007986:Luteinizing Hormone
AS; BSA; CGβ; CHO; CTP; Carboxyl-terminal peptide (CTP); Chinese hamster ovary; Evolution; LH; LHβ; O-glycans; PBS; antiserum; bo; bovine; bovine serum albumin; carboxyl-terminal peptide; h; hCG; human; human chorionic gonadotropin; lutropin; phosphate buffered saline; wild-type; wt