title: The GPCR repertoire in the demosponge Amphimedon queenslandica: insights into the GPCR system at the early divergence of animals.
abstract: BACKGROUND
  G protein-coupled receptors (GPCRs) play a central role in eukaryotic signal transduction. However, the GPCR component of this signalling system, at the early origins of metazoans is not fully understood. Here we aim to identify and classify GPCRs in Amphimedon queenslandica (sponge), a member of an earliest diverging metazoan lineage (Porifera). Furthermore, phylogenetic comparisons of sponge GPCRs with eumetazoan and bilaterian GPCRs will be essential to our understanding of the GPCR system at the roots of metazoan evolution.
  
  
  RESULTS
  We present a curated list of 220 GPCRs in the sponge genome after excluding incomplete sequences and false positives from our initial dataset of 282 predicted GPCR sequences obtained using Pfam search. Phylogenetic analysis reveals that the sponge genome contains members belonging to four of the five major GRAFS families including Glutamate (33), Rhodopsin (126), Adhesion (40) and Frizzled (3). Interestingly, the sponge Rhodopsin family sequences lack orthologous relationships with those found in eumetazoan and bilaterian lineages, since they clustered separately to form sponge specific groups in the phylogenetic analysis. This suggests that sponge Rhodopsins diverged considerably from that found in other basal metazoans. A few sponge Adhesions clustered basal to Adhesion subfamilies commonly found in most vertebrates, suggesting some Adhesion subfamilies may have diverged prior to the emergence of Bilateria. Furthermore, at least eight of the sponge Adhesion members have a hormone binding motif (HRM domain) in their N-termini, although hormones have yet to be identified in sponges. We also phylogenetically clarified that sponge has homologs of metabotropic glutamate (mGluRs) and GABA receptors.
  
  
  CONCLUSIONS
  Our phylogenetic comparisons of sponge GPCRs with other metazoan genomes suggest that sponge contains a significantly diversified set of GPCRs. This is evident at the family/subfamily level comparisons for most GPCR families, in particular for the Rhodopsin family of GPCRs. In summary, this study provides a framework to perform future experimental and comparative studies to further verify and understand the roles of GPCRs that predates the divergence of bilaterian and eumetazoan lineages.
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, Biomedical Center, Box 593, 75 124, Uppsala, Sweden. arunkumar.krishnan@neuro.uu.se.
authors.forename: Arunkumar
authors.initials: A
authors.lastname: Krishnan
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, Biomedical Center, Box 593, 75 124, Uppsala, Sweden. rohit.dnyansagar@gmail.com.|Department of Biotechnology, Indian Institute of Technology Madras, Chennai, 600036, India. rohit.dnyansagar@gmail.com.
authors.forename: Rohit
authors.initials: R
authors.lastname: Dnyansagar
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, Biomedical Center, Box 593, 75 124, Uppsala, Sweden. markus.almen@imbim.uu.se.
authors.forename: Markus Sällman
authors.initials: MS
authors.lastname: Almén
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, Biomedical Center, Box 593, 75 124, Uppsala, Sweden. michael.williams@neuro.uu.se.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Williams
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, Biomedical Center, Box 593, 75 124, Uppsala, Sweden. robert.fredriksson@neuro.uu.se.
authors.forename: Robert
authors.initials: R
authors.lastname: Fredriksson
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Madras, Chennai, 600036, India. nmanoj@iitm.ac.in.
authors.forename: Narayanan
authors.initials: N
authors.lastname: Manoj
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, Biomedical Center, Box 593, 75 124, Uppsala, Sweden. helgi.schioth@neuro.uu.se.
authors.forename: Helgi B
authors.initials: HB
authors.lastname: Schiöth
mesh_terms: D000818:Animals; D005075:Biological Evolution; D016678:Genome; D010802:Phylogeny; D011161:Porifera / Q000145:classification / Q000235:genetics*; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000235:genetics*; D012243:Rhodopsin / Q000235:genetics; D015398:Signal Transduction; D014714:Vertebrates / Q000235:genetics
chemical_list: D043562:Receptors, G-Protein-Coupled; D012243:Rhodopsin