Abstract
Nematodes and arthropods are the most speciose animal groups and possess Class 2 B1 G-protein coupled receptors (GPCRs). Existing models of invertebrate Class 2 B1 GPCR evolution are mainly centered on Caenorhabditis elegans and Drosophila melanogaster and a few other nematode and arthropod representatives. The present study reevaluates the evolution of metazoan Class 2 B1 GPCRs and orthologues by exploring the receptors in several nematode and arthropod genomes and comparing them to the human receptors. Three novel receptor phylogenetic clusters were identified and designated cluster A, cluster B and PDF-R-related cluster. Clusters A and B were identified in several nematode and arthropod genomes but were absent from D. melanogaster and Culicidae genomes, whereas the majority of the members of the PDF-R-related cluster were from nematodes. Cluster A receptors were nematode and arthropod-specific but shared a conserved gene environment with human receptor loci. Cluster B members were orthologous to human GCGR, PTHR and Secretin members with which they probably shared a common origin. PDF-R and PDF-R related clusters were present in representatives of both nematodes and arthropods. The results of comparative analysis of GPCR evolution and diversity in protostomes confirm previous notions that C. elegans and D. melanogaster genomes are not good representatives of nematode and arthropod phyla. We hypothesize that at least four ancestral Class 2 B1 genes emerged early in the metazoan radiation, which after the protostome-deuterostome split underwent distinct selective pressures that resulted in duplication and deletion events that originated the current Class 2 B1 GPCRs in nematode and arthropod genomes.
Highlights
In tetrapods, five main G protein-coupled receptor (GPCR) gene families have been identified and are characterized by the presence of seven helical transmembrane (TM) structures [1,2]
The Secretin-like family of G-protein coupled receptors (GPCRs), named after the receptor that binds to secretin, the first hormone identified in vertebrates [3,4,5], is known as Class 2 (II or B) subfamily B1 GPCRs (Class 2 B1) and their members are only activated by polypeptide hormones [6,7,8]
The H. contortus sequences were retrieved from the Sanger database, the M. incognita sequences were obtained from the INRA database and the sequences of C. elegans, T. spiralis, P. pacificus and B. malayi were retrieved from the Wormbase and NCBI databases
Summary
Five main G protein-coupled receptor (GPCR) gene families have been identified and are characterized by the presence of seven helical transmembrane (TM) structures [1,2]. Unique features of Class 2 B1 GPCRs are the presence of large N-terminal ligand-binding ectodomain (N-ted) that contain six conserved cysteines and several N-glycosylation motifs [17,18,19]. Their ligands are moderately large peptides that are members of distinct endocrine peptide families and the vertebrate receptors have been grouped into five subfamilies and include the receptors for: a) calcitonin (CALC) and calcitonin gene related peptide (CGRP), b) corticotropin hormone (CRH), c) parathyroid and related peptides (PTH and PTHrP), d) glucagon (GCG) and related peptides (GLP) and e) secretin (SCT), vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating polypeptide (PACAP) and growth hormone releasing hormone (GHRH). Receptor activation occurs when peptides interact with the N-terminal domain and TM loops and this triggers intracellular signaling via adenylate cyclase and/or an increase in calcium ions
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