Remarkable similarities between the hemichordate (Saccoglossus kowalevskii) and vertebrate GPCR repertoire

Abstract

Saccoglossus kowalevskii (the acorn worm) is a hemichordate belonging to the superphylum of deuterostome bilateral animals. Hemichordates are sister group to echinoderms, and closely related to chordates. S. kowalevskii has chordate like morphological traits and serves as an important model organism, helping developmental biologists to understand the evolution of the central nervous system (CNS). Despite being such an important model organism, the signalling system repertoire of the largest family of integral transmembrane receptor proteins, G protein-coupled receptors (GPCRs) is largely unknown in S. kowalevskii. Here, we identified 260 unique GPCRs and classified as many as 257 of them into five main mammalian GPCR families; Glutamate (23), Rhodopsin (212), Adhesion (18), Frizzled (3) and Secretin (1). Despite having a diffuse nervous system, the acorn worm contains well conserved orthologues for human Adhesion and Glutamate family members, with a similar N-terminal domain architecture. This is particularly true for genes involved in CNS development and regulation in vertebrates. The average sequence identity between the GPCR orthologues in human and S. kowalevskii is around 47%, and this is same as observed in couple of the closest vertebrate relatives, Ciona intestinalis (41%) and Branchiostoma floridae (~47%). The Rhodopsin family has fewer members than vertebrates and lacks clear homologues for 6 of the 13 subgroups, including olfactory, chemokine, prostaglandin, purine, melanocyte concentrating hormone receptors and MAS-related receptors. However, the peptide and somatostatin binding receptors have expanded locally in the acorn worm. Overall, this study is the first large scale analysis of a major signalling gene superfamily in the hemichordate lineage. The establishment of orthologue relationships with genes involved in neurotransmission and development of the CNS in vertebrates provides a foundation for understanding the evolution of signal transduction and allows for further investigation of the hemichordate neurobiology.

Keywords: ANF_receptor; BAI; CASR; CELSR; CHEM; Deuterostomes; EDG; EGF; EGF_CA; FZD; Frizzled; G protein; G-protein coupled receptor family C group 5 members; GABABs; GPCR Proteolytic site domain; GPRC5s; GPS; HCRTRs; HYR; ITR; Information exchange; LEC; LGR; MAS-related receptors; MCHR; MCR; MECA; MRG; MTN; NCD3G; Nervous system; Neurotransmission; OLF; OPN; PACAP; PTGER; PTHR; PUR; SMOH; SOG; SSTRs; TACR; TRHR; TSP1; VIPR; VLGR; VWD; atrial natriuretic peptide receptor; brain angiogenesis inhibitor; cAMP receptor; cadherin EGF LAG seven-pass G type receptors; calcium sensing receptor; calcium-binding epidermal growth factor domain; chemokine receptor; cyclic adenosine monophosphate receptor; endothelial differentiation GPCR; epidermal growth factor; gamma-aminobutyric acid type B receptors; hyalin repeat domain; intimal thickness related receptor; lectomedin receptors; leucine rich repeat containing GPCR; melanin concentrating hormone receptor; melanocortin receptors; melanocortin, endothelial differentiation, cannabinoid, adenosine GPCR cluster; melatonin receptors; nine cysteines domain of family 3 GPCR; olfactory receptors; opsin-like receptors; orexin receptors; parathyroid hormone receptor; pituitary adenylyl cyclase activating protein; prostaglandin receptor; purine; smoothened; somatostatin receptors; somatostatin, opioid, galanin cluster; tachykinin receptor; thrombospondin 1; thyrotropin-releasing Hormone receptor; vasoactive intestinal peptide receptor; very large G-Protein-coupled receptor; von Willebrand factor type D domain.