Journal of Heredity Advance Access originally published online on January 13, 2005
Journal of Heredity 2005 96(3):205-211; doi:10.1093/jhered/esi024
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© 2005 The American Genetic Association
Evolution of New Hormone Function: Loss and Gain of a Receptor
From the Department of Laboratory Medicine and Pathobiology, Banting and Best Diabetes Centre, University of Toronto, 100 College St., Toronto, Ontario, Canada M5G lL5
Address correspondence to David M. Irwin at the address above, or e-mail: david.irwin{at}utoronto.ca.
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Abstract |
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The vertebrate proglucagon gene encodes three glucagon-like sequences (glucagon, glucagon-like peptide-1 [GLP-1], and glucagon-like peptide 2 [GLP-2]) that have distinct functions in regulating metabolism in mammals. In contrast, glucagon and GLP-1 have similar physiological actions in fish, that of mammalian glucagon. We have identified sequences similar to receptors for proglucagon-derived peptides from the genomes of two fish (pufferfish and zebrafish), a frog (Xenopus tropicalis), and a bird (chicken). Phylogenetic analysis of the receptor sequences suggested an explanation for the divergent function of GLP-1 in fish and mammals. The phylogeny of our predicted and characterized receptors for proglucagon-derived peptides demonstrate that receptors for glucagon, GLP-1, and GLP-2 have an origin before the divergence of fish and mammals; however, fish have lost the gene encoding the GLP-1 class of receptors, and likely the incretin action of GLP-1. Receptors that bind GLP-1, but yield glucagon-like action, have been characterized in goldfish and zebrafish, and these sequences are most closely related to glucagon receptors. Both pufferfish and zebrafish have a second glucagon receptor-like gene that is most closely related to the characterized goldfish glucagon receptor. The phylogeny of glucagon receptor-like genes in fish indicates that a duplication of the glucagon receptor gene occurred on the ancestral fish lineage, and could explain the shared action of glucagon and GLP-1. We suggest that the binding specificity of one of the duplicated glucagon receptors has diverged, yielding receptors for GLP-1 and glucagon, but that ancestral downstream signaling has been maintained, resulting in both receptors retaining glucagon-stimulated downstream effects.
The vertebrate proglucagon gene encodes three glucagon-like sequences (glucagon, glucagon-like peptide-1 [GLP-1], and glucagon-like peptide-2 [GLP-2]) that have distinct functions regulating metabolism in mammals (Drucker 2001, 2002; Jiang and Zhang 2003; Kieffer and Habener 1999). Glucagon is a 29 amino acid hormone that is produced by the A cells of the pancreatic islets and is the counterregulatory hormone to insulin in maintaining energy balance (Jiang and Zhang 2003). Characterization of mammalian proglucagon genes (Bell et al. 1983; Heinrich et al. 1984) resulted in the identification of two additional glucagon-like sequences, GLP-1 and GLP-2, encoded by the proglucagon gene. Both GLP-1 and GLP-2 are secreted by mammalian intestinal L cells in response to food (Drucker 2001, 2002). In mammals, GLP-1 functions as an incretin hormone, potentiating the release of insulin from pancreatic B cells, and thus regulating glucose metabolism (Drucker 2001, 2002). In contrast, in fish, GLP-1 is secreted from both intestinal and pancreatic cells, and it has a biological activity similar to that of glucagon (Duguay and Mommsen 1994; Plisetskaya and Mommsen 1996). GLP-2 function has only been described in some mammals, where it acts as an intestinal growth factor, aiding in the maintenance of intestinal epithelial cell functions and with the ability to absorb nutrients through the digestive tract (Drucker 2001, 2002).
Despite the differences in biological activity of glucagon and the glucagon-like peptides, they are all derived from a common ancestral sequence (Irwin 2001; Irwin et al. 1999; Lopez et al. 1984). The glucagon-like sequences encoded by the proglucagon gene evolved prior to the earliest divergence of extant vertebrates, as all three are shared among vertebrate classes (Irwin 2001; Irwin et al. 1999). The proglucagon gene belongs to a larger gene family that includes the genes for glucose-dependent insulinotropic peptide (GIP), growth hormone releasing hormone (GHRH), pituitary adenylate cyclase activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), and secretin (SCT) (Sherwood et al. 2000). Each of these glucagon-like hormones has acquired unique and essential functions in vertebrate physiology.
Glucagon, GLP-1, GLP-2, and other glucagon-like hormones bind to unique, but related, G-protein-coupled receptors (Mayo et al. 2003). The receptors for the proglucagon-derived peptides, together with the receptor for the hormone GIP, form a subfamily of the secretin class (class B) of G-protein-coupled receptors (Harmar 2001; Joost and Methner 2002; Sivarajah et al. 2001). Receptors for the proglucagon-derived peptides, and for GIP, have been best characterized in mammalian species (Mayo et al. 2003), although glucagon receptors have been cloned from three species of frogs (Ngan et al. 1999; Sivarajah et al. 2001) and one species of fish (Chow et al. 2004), and GLP-1 receptors have been isolated from two species of fish (Mojsov 2000; Yeung et al. 2002). Intriguingly, it was reported that the fish GLP-1 receptors were more closely related to glucagon receptors (from fish, frogs, and mammals) than to mammalian GLP-1 receptors (Chow et al. 2004). To better understand the phylogenetic relationships between glucagon, GLP-1, GLP-2, and GIP receptors, and to gain insight into the origin of novel hormone functions, we have identified genes in genomes of two species of fish (pufferfish and zebrafish), a frog (Xenopus tropicalis), and the chicken that encode receptor sequences most similar to these receptors. The phylogeny of these receptors suggests an explanation for the differences in biological activity of GLP-1 in mammals and fish.
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Methods |
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Molecular Databases
Sequences for known receptors for proglucagon-derived peptides (glucagon, GLP-1, and GLP-2) as well as the receptors for GIP were downloaded from GenBank (http://www.ncbi.nlm.nih.gov/). Genome databases for chicken (Gallus gallus, version 1), pufferfish (Takifugu rubripes, build 2c), and zebrafish (Danio rerio, version 3), maintained by Ensemble (http://www.ensemble.org), and X. tropicalis (version 2.0), maintained by the U.S. Department of Energy Joint Genome Institute (http://www.jgi.doe.gov/index.html), were searched for sequences similar to mammalian glucagon, GLP-1, GLP-2, and GIP receptors. Searches of the genome databases initially used the tblastn algorithm to find genomic sequences that potentially encoded protein sequences similar to the receptor amino acid sequences. To complement genomic data, expressed sequence tag (EST) databases, at the Ensemble and Joint Genome Institute genome database sites, the National Center for Biotechnology Information (NCBI) (http://www.ncbi.nlm.nih.gov), and the University of Manchester Institute of Science and Technology Chicken EST database (http://www.chick.umist.ac.uk/) (Boardman et al. 2002) were searched for sequences similar to the glucagon/GLP-1/GLP-2/GIP receptors or for transcripts derived from genomic sequences identified in our earlier searches. Sequences with similarities to query sequences were downloaded and further characterized using MacDNASIS version 3.7 DNA and protein sequence analysis software (Hitachi, San Bruno, CA) using methods we have previously described (Irwin 2002; Irwin and Gong 2003; Zhou and Irwin 2004).
Molecular Sequence and Phylogenetic Analysis
Genomic structures (exons and introns) of genes for receptor were predicted from the genomic sequences using cDNAs or ESTs available from each species, or closely related species, or by comparing to alignments of proteins from diverse vertebrate species, essentially as previously described (Irwin 2002; Irwin and Gong 2003; Zhou and Irwin 2004). Intron-exon boundary consensus rules (e.g., AG/GT) were observed and the intron phase of homologous introns was maintained with those of the mammalian receptor genes. Predicted gene structures were used to infer cDNA sequences that were then translated into predicted protein sequences. Protein sequence alignments were generated using Clustal (Thompson et al. 1994), as implemented in MacDNASIS. Aligned sequences were edited to remove all ambiguously aligned amino acid residues prior to phylogenetic analysis, as previously described (Sivarajah et al. 2001). Phylogenies of protein sequences were estimated using PAUP*4.0b10, MEGA2, and MEGA3 (Kumar et al. 2001, 2004; Swofford 2002) using parsimony (with the PROTPARS matrix) and distance (e.g., neighbor-joining) methods (with Dayhoff or JTT distances). Our confidence in the phylogenies was assessed using 500 bootstrap replicates.
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Identification of Genomic Sequences Encoding Sequences Similar to Receptors for Proglucagon-Derived Peptides
Searches of fish (pufferfish, zebrafish), frog (X. tropicalis), and chicken genomic databases identified a number of genomic sequences with similarities to the sequences for receptors for proglucagon-derived peptides or GIP. Reciprocal blast searches (i.e., searches of annotated mammalian genomes with fish, frogs, or chicken genomic sequences) were used to eliminate genomic sequences most similar to other secretin class (class B) G-protein-coupled receptors (e.g., VIP, PACAP, and calcitonin receptors) (see Harmar 2001; Joost and Methner 2002). Genomic sequences encoding receptors that were more similar to glucagon-like receptors or were roughly equally similar to the glucagon-like and other secretin class receptors were further characterized to predict encoded receptor-like protein sequences. EST databases were also searched for similar sequences, with only the chicken EST databases yielding sequences with significant similarity to glucagon/GLP-1/GLP-2/GIP receptors. Identified chicken ESTs allowed prediction of a nearly full-length glucagon receptor-like cDNA and partial cDNA sequences for the GLP-1 and GLP-2 receptor-like genes. No ESTs for the GIP receptor-like gene were identified in the chicken EST databases. No ESTs from pufferfish, zebrafish, or Xenopus (tropicalis and laevis) with significant similarities to known glucagon/GLP-1/GLP-2/GIP receptors or our genomic sequences were identified. A total of 17 predicted receptor gene sequences were identified that had the greatest similarities to the glucagon/GLP-1/GLP-2/GIP receptors; 4 receptor gene sequences were predicted in pufferfish, zebrafish, and chicken, and 5 receptor gene sequences were predicted in X. tropicalis (Table 1). Due to incomplete nature of the genome databases, the limited number of ESTs, and the low conservation of the N-terminal and C-terminal regions of the receptors, many of the predicted sequences, especially those with the most similarity to GIP receptor, are incomplete (see Table 1).
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Phylogeny of Receptors for Proglucagon-Derived Peptides
After aligning our predicted receptor's amino acid sequences with previously identified glucagon, GLP-1, GLP-2, and GIP receptor sequences, we used phylogenetic methods to determine their genetic relationships. Previous work has shown that the glucagon, GLP-1, GLP-2, and GIP receptors form a monophyletic group within the secretin class of G-protein-coupled receptors (Chan et al. 1998; Chow et al. 1997; Harmer 2001; Joost and Methner 2002; Laburthe et al. 1996; Sivarajah et al. 2001). Our analysis of the diverse vertebrate receptor sequences showed that all of the new sequences grouped with the previously characterized glucagon, GLP-1, GLP-2, and GIP receptors, with vasoactive intestinal peptide (VIP) receptors as an outgroup, and that a group that included the mammalian GLP-2 receptors was the first diverging lineage within this group. The relationships of the mammalian glucagon, GLP-1, GLP-2, and GIP receptors were identical to those described in recent phylogenetic analysis, that is, the glucagon receptors are more closely related to GIP receptors than to GLP-1 receptors (Chow et al. 2004; Joost and Methner 2002; Sivarajah et al. 2001).
To maximize the amount of aligned amino acid sequence data, subsequent phylogenetic analysis used alignments without the VIP receptor sequences. For these analyses, the monophyletic group that included the mammalian GLP-2 receptors was used as the outgroup (Figure 1). We have used the mammalian receptors to classify each group of receptors (Figure 1 and Table 1). Again we found that the mammalian glucagon receptors were more closely related to GIP receptors than to GLP-1 receptors. The monophyly of the glucagon, GLP-1, and GLP-2 receptors was generally well supported (88–100% bootstrap support in both parsimony and neighbor-joining trees) and consistent with the expected phylogeny of the species, that is, the fish diverge first, followed by frogs, and then chicken (Figure 1), except for the poorly resolved position of the X. tropicalis GLP-2 receptor. The mammalian glucagon, GLP-2, and GIP receptors each were within monophyletic groups that included receptor sequences from fish, frogs, chicken, and mammals (Figure 1). The monophyly of the GIP receptors is the least well supported, and in some of our analyses with other outgroups, formed two monophyletic groups, the two primary branches of this group, although in none of our analyses did any of the GIP receptor-like sequences group with the glucagon, GLP-1, or GLP-2 receptors (see Figure 1). In addition, the species phylogeny of the GIP receptors does not agree with the accepted phylogeny of vertebrates or of the other groups of receptors. It should be noted that the GIP receptor-like sequences are made up of sequences that were less complete, and in the case of the chicken, were generated by splicing together multiple genomic contigs (Table 1). The low support and poor resolution are likely due to the incomplete nature of these sequences.
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A total of four receptors have been predicted in the chicken genome, and these sequences are represented in each of the four monophyletic groups of receptors (Figure 1). For the glucagon, GLP-1, and GLP-2 groups of receptors, the chicken sequences represent, as expected, the receptor most closely related to the mammalian receptor sequences (Figure 1). A total of five receptor sequences were identified in X. tropicalis genome, although we used the glucagon receptor sequence from the closely related X. laevis in the phylogenetic analysis due to the incomplete nature of the X. tropicalis glucagon receptor gene sequence (Table 1). The glucagon, GLP-1, and GLP-2 receptors were identified as single copy, while two GIP receptor-like genes were found in the X. tropicalis genome (Figure 1). In both pufferfish and zebrafish, four gene sequences similar to mammalian glucagon/GLP-1/GLP-2/GIP receptors were found (Table 1). Phylogenetic analysis grouped these receptors into three of the mammalian receptor groups, the glucagon, GLP-2, and GIP receptors. A pair of receptors in pufferfish, zebrafish, and goldfish, including the previously characterized zebrafish and goldfish GLP-1 receptors, grouped with the mammalian and frog glucagon receptors. None of our predicted fish receptors grouped with mammalian GLP-1 receptors (Figure 1).
Fish GLP-1 Receptors
An unexpected observation of our phylogenetic analysis was the absence of GLP-1 receptor-like sequence in fish and that the characterized goldfish and zebrafish GLP-1 receptors (Mojsov 2000; Yeung et al. 2002) were within the glucagon type rather than the GLP-1 type of receptors (Figure 1). Indeed, the fish GLP-1 receptors were most closely related, with 100% bootstrap support, to the goldfish glucagon receptor (Chow et al. 2004) than to any other characterized receptor. While there are two receptors of the glucagon type in fish genomes, we were unable to identify any sequences in either the pufferfish or zebrafish genome that were more closely related to GLP-1 receptors than to any other receptor gene (Figure 1 and Table 1). All of the fish glucagon-type receptors were more closely related to each other than to other receptors, and the phylogeny suggested that they were the product of a gene duplication event on the fish lineage before the divergence of the different fish species (see Figure 1). The duplication of a glucagon class receptor is consistent with a proposed genome duplication event on the fish lineage that should have generated two copies of every gene in the ancestral fish genome (Amores et al. 1998; Aparicio 2000).
The phylogeny in Figure 1 indicates that the GLP-1 type of receptors diverged from the glucagon receptor gene before the divergence of fish and mammals, indicating that the ancestor to fish and mammals had both glucagon and GLP-1 (and GLP-2 and GIP) types of receptor genes. This suggests that the gene orthologous to the mammalian GLP-1 receptor has been lost in the fish lineage. The loss of the GLP-1-type receptor gene likely occurred before the proposed fish genome duplication event, and the divergence of pufferfish and zebrafish, otherwise two or more independent losses of the GLP-1 receptor gene need to be proposed.
A Model for the Evolution of Fish GLP-1 Function
The phylogeny of receptors for proglucagon-derived peptides suggests a possible explanation for the differences in biological function of GLP-1 in fish and mammals, and predicts its function in frogs and birds. In mammals, GLP-1 is an incretin hormone that acts to potentiate the release of insulin from pancreatic B cells (Drucker 2001, 2002). Insulin then acts to lower blood glucose levels. In fish, GLP-1 activity is opposite to that in mammals. In fish, GLP-1 acts like glucagon on the liver to increase blood glucose levels (Duguay and Mommsen 1994; Plisetskaya and Mommsen 1996). Our previous comparison of the phylogenies of glucagon-like sequences and receptors for these peptides suggested to us that receptor-ligand specificity evolved after duplication of both peptides and receptors, yielding incongruent phylogenies (Sivarajah et al. 2001). Given our limited phylogeny of the receptors, and the fact that glucagon and GLP-1 have very similar functions in fish, we further suggested that the ancestral function of glucagon, GLP-1, and GIP was similar to glucagon, and that each of these ligands may have bound to multiple receptors, and that GLP-1 and GIP acquired their unique incretin functions on the lineage leading to mammals after the fish–mammal divergence (Sivarajah et al. 2001). Subsequent characterization of the goldfish GLP-1 receptor suggested support for this model, as the GLP-1 receptor could bind both glucagon and GLP-1 (Chow et al. 2004; Yeung et al. 2002).
A problem with our model, though, was that we needed a change in tissue-specific gene expression of the receptor (from liver to pancreatic islet cells) to occur in parallel to the evolution of specificity in ligand binding. We did recognize that the characterization of receptors for glucagon-like sequences from diverse vertebrates should help resolve our understanding of the evolution of the distinct biological functions. Our new phylogenetic analysis of receptors similar to the mammalian glucagon, GLP-1, GLP-2, and GIP receptors leads us to suggest an alternative, and we believe simpler, hypothesis for the evolution of the different function of GLP-1 in fish and mammals, but it also supports our original hypothesis that receptor-ligand specificity evolved well after the origin of the multiple glucagon-like sequences and multiple receptor genes.
We could not identify a homologue of the mammalian GLP-1 receptor in either the pufferfish or zebrafish genomes. Previously we had assumed that a GLP-1 receptor homologous to mammalian GLP-1 receptors existed in fish, but that it generated an action like glucagon. We now conclude that fish do not have mammalian (incretin) GLP-1 action because they do not have a GLP-1 receptor homologous to mammalian GLP-1 receptors that could generate an incretin-like action. The existence of GLP-1 receptors in X. tropicalis and chicken homologous to mammalian GLP-1 receptors leads us to suggest that in these species GLP-1 acts as an incretin hormone. The similarity of the glucagon and GLP-1 action in fish can be explained by the observation that the receptors that bind GLP-1 in fish are most closely related to glucagon receptors (Figure 1). The fish GLP-1 receptor was generated by a gene duplication event, likely part of the fish genome duplication event. We suggest that it was after duplication of the glucagon receptor gene, but before radiation of teleost fish, that one of the duplicated glucagon receptors acquired the ability to bind, and be activated by, GLP-1. We suspect that the duplicated glucagon acquired the ability to bind GLP-1 before the radiation of teleost fish because GLP-1 has glucagon activity in all teleost fish species examined (Duguay and Mommsen 1994; Mommsen et al. 2001; Plisetskaya and Mommsen 1996). We therefore also predict that the pufferfish glucagon receptor 2 will bind, and be activated by, GLP-1 (see Figure 1). Both the glucagon and GLP-1 receptors are duplicates of an ancestral glucagon receptor that was expressed in the liver and generated signals that generate glucagon actions. The duplicated receptors have conserved the site of expression (i.e., liver) and downstream signaling properties, despite divergence in ligand binding. Thus the binding of two different ligands (glucagon or GLP-1) will generate similar responses.
Our new model also explains why the goldfish GLP-1 receptor (Yeung et al. 2002), but not the goldfish glucagon receptor (Chow et al. 2004) has the ability to bind to both glucagon and GLP-1. We hypothesize that the GLP-1 receptor (Yeung et al. 2002) was a "glucagon" receptor that gained the ability to bind GLP-1, but has not lost the ability to bind glucagon. In contrast, the characterized glucagon receptor (Chow et al. 2004) has always been specific for glucagon. Species-specific differences in the levels of expression of glucagon and GLP-1 receptor genes, together with species-specific variations in ligand binding specificity, likely explain why glucagon is the major glycogenolytic hormone (i.e., the hormone the regulates the production of glucose from glycogen in the liver) in some fish species, while in others, GLP-1 is the major glycogenolytic hormone (see Mommsen et al. 2001).
Origin of Receptors for Proglucagon-Derived Peptides
The acquisition of the ability to bind and be activated by GLP-1 by a duplicate of the glucagon receptor on the fish lineage demonstrates that ligand-receptor specificity for receptors for proglucagon-derived peptides can change. This supports our earlier model that explained the lack of concordance between the phylogeny of the glucagon-like sequences encoded by the proglucagon gene and the phylogeny of the receptors for these peptides (Sivarajah et al. 2001). We hypothesized that the evolution of ligand-receptor specificity evolved well after the initial duplication of the glucagon-like sequences and receptors rather than by coevolution of ligand-receptor pairs. The evolution of the GLP-1 receptors in fish, by a glucagon receptor acquiring the ability to bind GLP-1, provides further support for our model for the evolution of the receptors for proglucagon-derived peptides.
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Acknowledgments |
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This work was supported by a grant from the Natural Sciences and Engineering Research Council. This paper is based on a presentation at the symposium entitled "Genomes and Evolution 2004," cosponsored by the American Genetic Association and the International Society of Molecular Biology and Evolution at The Pennsylvania State University, State College, PA, June 17–20, 2004.
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Corresponding Editor: Shozo Yokoyama
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Amores A, Force A, Yan YL, Joly L, Amemiya C, Fritz A, Ho RK, Langeland J, Prince V, Wang YL, Westerfield M, Ekker M, and Postlethwait JH, 1998. Zebrafish hox clusters and vertebrate genome evolution. Science 282:1711–1714.
Aparicio S, 2000. Vertebrate evolution: recent perspectives from fish. Trends Genet 16:54–56.[CrossRef][ISI][Medline]
Bell GI, Sanchez-Pescador R, Laybourn PJ, and Najarian RC, 1983. Exon duplication and divergence in the human preproglucagon gene. Nature 304:368–371.[CrossRef][Medline]
Boardman PE, Sanz-Ezquerro J, Overton IM, Burt DW, Bosch E, Fong WT, Tickle C, Brown WRA, Wilson SA, and Hubbard SJ, 2002. A comprehensive collection of chicken cDNAs. Curr Biol 12:1965–1969.[CrossRef][ISI][Medline]
Chan K-W, Yu K-L, Rivier J, and Chow BK-C, 1998. Identification and characterization of a receptor from goldfish specific for a teleost growth hormone-releasing hormone-like peptide. Neuroendocrinology 68:44–56.[CrossRef][ISI][Medline]
Chow BKC, Yeun TT-H, and Chan K-W, 1997. Molecular evolution of vertebrate VIP receptors and functional characterization of a VIP receptor from Carassius auratus. Gen Comp Endocrinol 105:176–185.[CrossRef][ISI][Medline]
Chow BKC, Moon TW, Hoo RLC, Yeung C-M, Müller M, Christos PJ, and Mojsov S, 2004. Identification and characterization of a glucagon receptor from the goldfish Carassius auratus: implications for the evolution of the ligand specificity of glucagon receptors in vertebrates. Endocrinology 145:3273–3288.
Drucker DJ, 2001. The glucagon-like peptides. Endocrinology 142:521–527.
Drucker DJ, 2002. Biological actions and therapeutic potential of the glucagon-like peptides. Gastroenterology 122:531–544.[CrossRef][ISI][Medline]
Duguay SJ and Mommsen TP, 1994. Molecular aspects of pancreatic peptides In: Fish physiology, vol. 13 (Hoar WS and Randall DJ, eds). San Diego: Academic Press: 225–271.
Harmar AJ, 2001. Family-B G-protein-coupled receptors. Genome Biol 2:3013.1–3013.10.
Heinrich G, Gros D, and Habener JF, 1984. Glucagon gene sequence, four of six exons encode separate genetic domains of rat pre-proglucagon. J Biol Chem 259:14082–14087.
Irwin DM, 2001. Molecular evolution of proglucagon. Regul Pept 98:1–12.[CrossRef][ISI][Medline]
Irwin DM, 2002. Ancient duplications of the human proglucagon gene. Genomics 79:741–746.[CrossRef][ISI][Medline]
Irwin DM and Gong Z, 2003. Molecular evolution of vertebrate goose-type lysozyme genes. J Mol Evol 56:234–242.[CrossRef][ISI][Medline]
Irwin DM Huner O, and Youson JH, 1999. Lamprey proglucagon and the origin of glucagon-like peptides. Mol Biol Evol 16:1548–1557.[Abstract]
Jiang G and Zhang BB, 2003. Glucagon and regulation of glucose metabolism. Am J Physiol 284:E671–E678.
Joost P and Methner A, 2002. Phylogenetic analysis of 277 human G-protein-coupled receptors as a tool for the prediction of orphan receptor ligands. Genome Biol 3:0063.1–0063.16.
Kieffer TJ and Habener JF, 1999. The glucagon-like peptides. Endocr Rev 20:876–913.
Kumar S, Tamura K, Jakobsen IB, and Nei M, 2001. MEGA2: molecular evolutionary genetics analysis software. Bioinformatics 17:1244–1245.
Kumar S, Tamura K, and Nei M, 2004. MEGA3: integrated software for molecular evolutionary genetics analysis and sequence alignment. Brief Bioinform 5:150–163.
Laburthe M, Couvineau A, Gaudin P, Maoret J-J, Rouyer-Fessard C, and Nicole P, 1996. Receptors for VIP, PACAP, secretin, GRF, glucagon, GLP-1, and other members of their new family of G protein-linked receptors: structure-function relationships with special reference to the human VIP-1 receptor. Ann N Y Acad Sci 805:94–109.[ISI][Medline]
Lopez LC, Li W-H, Frazier ML, Luo C-C, and Saunders GF, 1984. Evolution of glucagon genes. Mol Biol Evol 1:335–344.[Abstract]
Mayo KE, Miller LJ, Bataille D, Dalle S, Göke B, Thorens B, and Drucker DJ, 2003. International Union of Pharmacology. XXXV. The glucagon receptor family. Pharmacol Rev 55:167–194.
Mojsov S, 2000. Glucagon-like peptide-1 (GLP-1) and the control of glucose metabolism in mammals and teleost fish. Am Zool 40:246–258.[CrossRef]
Mommsen TP, Conlon JM, and Irwin DM, 2001. Amphibian glucagon family peptides: potent metabolic regulators in fish hepatocytes. Regul Pept 99:111–118.[CrossRef][ISI][Medline]
Ngan ESW, Chow LSN, Tse DLK, Du X, Wei Y, Mojsov S, and Chow BKC, 1999. Functional studies of a glucagon receptor isolated from frog Rana tigrina rugulosa: implications on the molecular evolution of glucagon receptors in vertebrates. FEBS Lett 457:499–504.[CrossRef][ISI][Medline]
Plisetskaya EM and Mommsen TP, 1996. Glucagon and glucagon-like peptides in fishes. Int Rev Cytol 168:187–257.[ISI][Medline]
Sherwood NM, Krueckl SL, and McRory JE, 2000. The origin and function of the pituitary adenylate cyclase-activating polypeptide (PACAP)/glucagon superfamily. Endocr Rev 21:619–670.
Sivarajah P, Wheeler MJ, and Irwin DM, 2001. Evolution of receptors for proglucagon-derived peptides: isolation of frog glucagon receptors. Comp Biochem Physiol 128B:517–527.
Swofford DL, 2002. PAUP*: phylogenetic analysis using parsimony (*and other methods), version 4.0b10 Sunderland, MA: Sinauer Associates.
Thompson JD, Higgins DG, and Gibson TJ, 1994. CLUSTAL W: improving the sensitivity of progressive multiple alignment through sequence weighting, position-specific gap penalties and weight matrix choices. Nucleic Acids Res 22:4373–4380.
Yeung C-M, Mojsov S, Mok P-Y, and Chow BKC, 2002. Isolation and structure-function studies of a glucagon-like peptide 1 receptor from goldfish Carassius auratus: identification of three charged residues in extracellular domains critical for receptor function. Endocrinology 143:4646–4654.
Zhou L and Irwin DM, 2004. Fish proglucagon genes have differing coding potential. Comp Biochem Physiol 137B:255–264.
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