Variation in the rates of evolution of the insulin and glucagon hormone and receptor genes in rodents

Abstract

Insulin and glucagon are important hormones for regulating blood glucose levels. Rodents are useful models for understanding human physiology, however, differences exist between rodents and humans. Here I examined the evolution of the genes encoding insulin (Ins) and glucagon (Gcg, which also encodes GLP-1 and GLP-2) and the receptors for these hormones (Insr, Gcgr, Glp1r, and Glp2r). Our results show that the insulin 1 gene (Ins1) that originated by retroposition in some rodents such as mice, experienced selective constraints that are as strong as those acting upon the Ins2 gene found in the locus-of-origin. Previous studies had shown that the insulin hormones and genes in hystricomorph rodents, such as the guinea pig, have altered function and selective constraints, respectively. Here I show that the insulin receptor genes in hystricomorph rodents also experienced changes in evolutionary rates, but that these changes did not alter sites involved in hormone binding. While glucagon, but not GLP-1 and GLP-2, in hystricomorph rodents also show increased rates of sequence evolution, no changes in the evolution of the glucagon receptor gene (Gcgr) was seen. Intriguingly, the GLP2 receptor gene (Glp2r) in mice-like rodents evolved more rapidly than those in hystricomorph rodents. When the rates of evolution of the genes encoding the receptors for proglucagon-derived peptides, which are all G-protein coupled receptors, were compared, the GLP-1 receptor gene (Glp1r) was found to display increased levels of sequence constraint compared to the Gcgr and Glp2r genes.