Volume 526, Issue 2, 10 September 2013, Pages 122–133
Remarkable similarities between the hemichordate (Saccoglossus kowalevskii) and vertebrate GPCR repertoire
- Department of Neuroscience, Functional Pharmacology, Uppsala University, BMC, Box 593, 751 24 Uppsala, Sweden
Highlights
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First analysis of a major superfamily of signalling genes in hemichordate lineage
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Found representatives for each of the five main mammalian GPCR GRAFS families
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List of orthologues involved in CNS regulation and development in vertebrate species
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Highly conserved orthologues for Adhesion and Glutamate GPCR families
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.
Abbreviations
- ANF_receptor, atrial natriuretic peptide receptor;
- BAI, brain angiogenesis inhibitor;
- cAMP receptor, cyclic adenosine monophosphate receptor;
- CASR, calcium sensing receptor;
- CELSR, cadherin EGF LAG seven-pass G type receptors;
- CHEM, chemokine receptor;
- EDG, endothelial differentiation GPCR;
- EGF,epidermal growth factor;
- EGF_CA, calcium-binding epidermal growth factor domain;
- FZD, Frizzled;
- GABABs, gamma-aminobutyric acid type B receptors;
- GPRC5s, G-protein coupled receptor family C group 5 members;
- GPS, GPCR Proteolytic site domain;
- HCRTRs, orexin receptors;
- HYR, hyalin repeat domain;
- ITR, intimal thickness related receptor;
- LEC, lectomedin receptors;
- LGR, leucine rich repeat containing GPCR;
- MCHR, melanin concentrating hormone receptor;
- MCR, melanocortin receptors;
- MECA,melanocortin, endothelial differentiation, cannabinoid, adenosine GPCR cluster;
- MTN, melatonin receptors;
- MRG, MAS-related receptors;
- NCD3G, nine cysteines domain of family 3 GPCR;
- OLF, olfactory receptors;
- OPN, opsin-like receptors;
- PACAP, pituitary adenylyl cyclase activating protein;
- PTGER,prostaglandin receptor;
- PTHR, parathyroid hormone receptor;
- PUR, purine;
- SMOH, smoothened;
- SOG,somatostatin, opioid, galanin cluster;
- SSTRs, somatostatin receptors;
- TACR, tachykinin receptor;
- TRHR,thyrotropin-releasing Hormone receptor;
- TSP1, thrombospondin 1;
- VIPR, vasoactive intestinal peptide receptor;
- VLGR, very large G-Protein-coupled receptor;
- VWD, von Willebrand factor type D domain
Keywords
- Neurotransmission;
- G protein;
- Information exchange;
- Deuterostomes;
- Nervous system
Figures and tables from this article:
- Fig. 1. Schematic presentation of GPCRs found in S. kowalevskii. The illustration shows comparisons of GPCRs found in S. kowalevskii, C. intestinalis, B. floridae, S. purpuratus, and human. The representation of the tree and the classifications of GPCRs are adopted from Fredriksson et al. (2003) and updated according to Nordstrom et al. (2011).Dictyostelium cAMP receptor family is shown as a red star to represent that they are the ancestor (Nordstrom et al., 2011). The Glutamate family, GPR-108 like, and ITR-like families were separated as they evolved separately (Nordstrom et al., 2011). Each coloured circle represents the species. The numbers within every coloured circle represents the GPCRs found in each of the families. The numbers above each coloured circle represent how many of those identified GPCRs unambiguously cluster with the human GPCRs in the phylogenetic trees. The number of GPCRs in each family for human was obtained from Fredriksson and Schioth (2005) and Fredriksson et al. (2003), B.floridae from (Nordstrom et al., 2008) and C. intestinalis from (Kamesh et al., 2008). The lower part of the illustration shows the distribution of GPCR families in Homo sapiens, B. floridae, C. intestinalis, S. kowalevskii and S. purpuratusdisplayed on a logarithmic scale. The abbreviated families are OA, Ocular albinism receptors; VR, Vomeronasal receptors. The Rhodopsin family is further split into four major α-, β-, γ- and δ-groups and subgroups (see Abbreviations). The group “Others” on the pie chart denotes GPR-108 like, ITR-like, cAMP and Ocular albinism receptors.
- Fig. 2. Phylogenetic relationships and comparisons of N-terminal functional domains of Adhesion and Secretin GPCRs inS. kowalevskii and human. The tree is based on Bayesian method of phylogenetic inference. The phylogenetic tree is based only on the transmembrane region. Robustness of the nodes is tested with posterior probabilities based on MCMC analysis (see Materials and methods). The strength of the nodes supported by posterior probabilities is marked with distinct colours. The domains were identified with Pfam search with a cut-off E-value of 0.1. Each domain is represented with a coloured shape. The numbers at the corner of each connective thread along the domain symbols indicates the length of the N-termini.
- Fig. 3. Phylogenetic relationships and the presentation of the N-terminal functional domains of the Glutamate GPCRs inS. kowalevskii and human. This unrooted phylogenetic tree shows the topology supported by Bayesian analysis. The topology supports the presence of representatives of GRMs, GABABs, CASR-like and GPR158 in S. kowalevskii. The N-terminal domains were identified with Pfam search with a cut-off E-value of 0.1. The nodes supported by posterior probabilities are marked with distinct colours based on their strength. The numbers at the top of each connective thread along the domain symbols indicates the length of the N-termini. Each domain is marked with a symbol and abbreviated in the lower right corner.
- Fig. 4. Phylogenetic relationships between amine GPCRs in S. kowalevskii and human. The unrooted phylogenetic tree exemplifies the presence of unambiguous orthologues for most of the human amine receptors. The branches that indicate the presence of clear representatives were coloured. The strength of the nodes supported by posterior probabilities is marked with distinct colours. The illustration also demonstrates few divergent, species specific or fast evolving amine receptors in S. kowalevskii that lack reliable support from the phylogeny to be assigned as clear orthologues to a respective amine family in human. Except the protein sequences that are marked with the # symbols, all the other transcripts has the first five hits as amine GPCRs in a BLAST search against the tagged human GPCRs.
- Fig. 5. Phylogenetic relationships between peptide GPCRs in S. kowalevskii and human. The unrooted topology supports the presence of unambiguous orthologues for most of the human peptide receptors. Except the protein sequences that are marked with the # symbols, all the other transcripts has the first five hits as peptide GPCRs in a BLAST search against the tagged human GPCRs.
- Fig. S1. Phylogenetic relationships between SOG subgroup GPCRs in S. kowalevskii and human. The unrooted topology supports the presence of diverse set of SOG subgroup GPCRs in S. kowalevskii.
- Fig. S2. Phylogenetic relationships between Frizzled GPCRs in S. kowalevskii and human.
- Fig. S3. Conservation pattern of each of the genes (reported in Table 1) across C. Intestinalis, B. floridae and S.purpuratus.
- Table 1. List of GPCR orthologues in S. kowalevskii that are involved in CNS regulation or development in vertebrates.
- Note: The accession numbers that are given within parenthesis corresponds to the gene renamed above. Table 1 with complete references is provided in Supplementary data 2.
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- Corresponding author at: Department of Neuroscience, Biomedical Center, Box 593, 75 124 Uppsala, Sweden. Fax: + 46 18 51 15 40.
Copyright © 2013 Published by Elsevier B.V.
