title: Lamprey proglucagon and the origin of glucagon-like peptides.
abstract: We characterized two proglucagon cDNAs from the intestine of the sea lamprey Petromyzon marinus. As in other vertebrates, sea lamprey proglucagon genes encode three glucagon-like sequences, glucagon, and glucagon-like peptides 1 and 2 (GLP-1 and GLP-2). This observation indicates that all three glucagon-like sequences encoded by the proglucagon gene originated prior to the divergence of jawed and jawless vertebrates. Estimates of the rates of evolution for the glucagon-like sequences suggest that glucagon originated first, about 1 billion years ago, while GLP-1 and GLP-2 diverged from each other about 700 MYA. The two sea lamprey intestinal proglucagon cDNAs have differing coding potential. Proglucagon I cDNA encodes the previously characterized glucagon and the glucagon-like peptide GLP-1, while proglucagon II cDNA encodes a predicted GLP-2 and, possibly, a glucagon. The existence of two proglucagon cDNAs which differ with regard to their potential to encode glucagon-like peptides suggests that the lamprey may use differential gene expression as a third mechanism, in addition to alternative proteolytic processing and mRNA splicing, to regulate the production of proglucagon-derived peptides.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Ontario, Canada. david.irwin@utoronto.ca
authors.forename: D M
authors.initials: DM
authors.lastname: Irwin
authors.forename: O
authors.initials: O
authors.lastname: Huner
authors.forename: J H
authors.initials: JH
authors.lastname: Youson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary; D019143:Evolution, Molecular; D005934:Glucagon / Q000235:genetics*; D052216:Glucagon-Like Peptide 1; D053767:Glucagon-Like Peptide 2; D006801:Humans; D007798:Lampreys / Q000235:genetics*; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics*; D052336:Proglucagon; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D017386:Sequence Homology, Amino Acid
chemical_list: D018076:DNA, Complementary; D053767:Glucagon-Like Peptide 2; D010455:Peptides; D011498:Protein Precursors; D012333:RNA, Messenger; D052336:Proglucagon; D052216:Glucagon-Like Peptide 1; D005934:Glucagon