Journal of Molecular Endocrinology

Phylogeny and exon structures of GCG and related peptide genes. (A) Exon structures of the GCG and related genes from various vertebrates and lamprey. In this diagram, as only the open reading frame-encoding exons are counted, the first exon contains the signal peptide (SP) sequence. The exons that do not encode the mature peptide sequence are also shown as simple lines. GCG, GLP1, and GLP2 are encoded by three different exons of the human GCG gene. The Xenopus GCG gene encodes three independent GLP1 peptides as well as GCG and GLP2. The second forms of medaka and zebrafish GCG genes lack GLP2. Location of the mature peptides on the exons of other peptide genes such as GIP, GCRP, ADCYAP1, VIP, SCT, and GHRH is also shown. Nonmammalian ADCYAP1 and VIP encode PACAP-related peptide (PRP) and VIP-related peptide (VRP), respectively, while those sequences in human genes are dysfunctional. The vestiges that remained in the human genes are indicated by spaces covered with gray dashed lines. (B) Maximum likelihood phylogenetic tree for GLP1-related peptides of human (hu), mouse (mo), chicken (ch), anole lizard (an), Xenopus (xe), zebrafish (zf), medaka (md), fugu (fu), stickleback (sb), tetraodon (to), and lamprey (lam) along with human SCT, GHRH, VIP, and PACAP are shown. The mature peptide sequences were aligned using MUSCLE, and a bootstrap consensus tree was constructed using MEGA 5.05. Bootstrap numbers represent 100 replicates.