After the origin of the family
After the origin of the family of genes for receptors for peptides similar to glucagon, the genes have not remained static. Not only have their sequences evolved, but also like peptides similar to glucagon (Irwin, 2001, Irwin, 2009, Irwin, 2012, Ng et al., 2010, Hwang et al., 2013), the numbers of genes for the receptors has changed on different vertebrate lineages (Irwin and Wong, 2005, Ng et al., 2010, Irwin and Prentice, 2011, Hwang et al., 2013). The Glp1r gene was lost on the lineage leading to teleost fish before the fish-specific genome duplication, but then this genome Zebularine lead to the generation of a redundant Gcgr genes, one of which gained the ability to be bound and activated by GLP-1, resulting in a change in the function of GLP-1 (Chow et al., 2004, Irwin and Wong, 2005). Similarly, Gipr has been lost on the bird lineage, while the Gip gene, encoding its ligand, has been retained (Irwin and Zhang, 2006), suggesting that GIP may interact with a different receptor in birds, and thus likely has a different physiological function. In contrast, the Grlr gene was lost on the mammalian lineage, likely in parallel with the loss of the gene for its ligand. These gene losses should have resulted in the loss of the physiological function of the ortholog of exendin.
Acknowledgments Work from the author’s lab has been supported by Grants from the Natural Sciences and Engineering Research Council and the Canadian Institutes for Health Research.