Insights into the evolution of proglucagon‐derived peptides and receptors in fish and amphibians

Abstract

Glucagon and the glucagon-like peptides (GLP-1 and GLP-2) share a common evolutionary origin and are triplication products of an ancestral glucagon exon. In mammals, a standard scenario is found where only a single proglucagon-derived peptide set exists. However, fish and amphibians have either multiple proglucagon genes or exons that are likely resultant of duplication events. Through phylogenetic analysis and examination of their respective functions, the proglucagon ligand-receptor pairs are believed to have evolved independently before acquiring specificity for one another. This review will provide a comprehensive overview of current knowledge of proglucagon-derived peptides and receptors, with particular focus on fish and amphibian species.

Incretin hormones and the expanding families of glucagon‐like sequences and their receptors

“…The zebrafish GIPR has been shown to functionally bind GIP. We, and others, were unable to identify a Gipr in the other fish genomes (Table 1) [28,35,36] and similar results have been reported for the Gip gene, where Gip sequences have only been found in the zebrafish genome and salmon cDNA [18,34,36]. Intriguingly, no near full‐length Gipr could be identified in any of the four available bird genomes (Table 1).…”

“…It has been suggested recently that fish genomes do contain a gene orthologous to mammalian Glp1r [28]. This conclusion was drawn from an analysis of a more complete set of receptor genes from diverse vertebrate species and was strengthened by the claim that the putative fish Glp1r was in a genomic neighbourhood that was conserved with amphibians and was linked to genes that are on the same chromosome that encodes mouse Glp1r [28].…”

“…Fish glucagon‐like peptide (GLP)‐1 receptors ( Glp1r ) are derived from glucagon receptors ( Gcgr ) and have only been described in goldfish and zebrafish, but likely include additional fish as indicated by the dotted line. GLP‐2 receptors ( Glp2r ) were used as the outgroup to root the tree as they were shown to the most divergent lineage in this subfamily in previous analyses [24–28].…”

“…The species phylogeny of Grlr , like the other receptors, is consistent with vertebrate phylogeny indicating that it diverged from Gcgr , Glp1r , Glp2r and Gipr subfamily prior to the divergence of fish and mammals. The recent study by Ng et al [28] had identified some of these sequences, those from fish, but in their analysis they were grouped with Glp1r . Given the conflicting results in the placement of Grlr additional analyses are required to confirm their validity as a separate group of receptors.…”

Molecular cloning of a proglucagon in a cyprinid fish (Schizothorax prenanti): mRNA tissue distribution and quantification during periprandial changes and fasting

“…In contrast, due to genome duplication, fish have duplicate proglucagon genes that generate multiple mRNA transcripts (Irwin and Wong, 1995;Zhou and Irwin, 2004). Proglucagon or PGDPs have been reported in several groups of fish (Ng et al, 2010). In fish, evidence has shown that GLP-1 and other PGDPs may affect feeding and energy homeostasis (Mommsen and Moon, 1989;Mojsov, 2000;Silverstein et al, 2001;Polakof et al, 2011).…”