title: Coevolution of the spexin/galanin/kisspeptin family: Spexin activates galanin receptor type II and III.
abstract: The novel neuropeptide spexin (SPX) was discovered using bioinformatics. The function of this peptide is currently under investigation. Here, we identified SPX along with a second SPX gene (SPX2) in vertebrate genomes. Syntenic analysis and relocating SPXs and their neighbor genes on reconstructed vertebrate ancestral chromosomes revealed that SPXs reside in the near vicinity of the kisspeptin (KISS) and galanin (GAL) family genes on the chromosomes. Alignment of mature peptide sequences showed some extent of sequence similarity among the 3 peptide groups. Gene structure analysis indicated that SPX is more closely related to GAL than KISS. These results suggest that the SPX, GAL, and KISS genes arose through local duplications before 2 rounds (2R) of whole-genome duplication. Receptors of KISS and GAL (GAL receptor [GALR]) are phylogenetically closest among rhodopsin-like G protein-coupled receptors, and synteny revealed the presence of 3 distinct receptor families KISS receptor, GALR1, and GALR2/3 before 2R. A ligand-receptor interaction study showed that SPXs activate human, Xenopus, and zebrafish GALR2/3 family receptors but not GALR1, suggesting that SPXs are natural ligands for GALR2/3. Particularly, SPXs exhibited much higher potency toward GALR3 than GAL. Together, these results identify the coevolution of SPX/GAL/KISS ligand genes with their receptor genes. This study demonstrates the advantage of evolutionary genomics to explore the evolutionary relationship of a peptide gene family that arose before 2R by local duplications.
authors: Graduate School of Medicine (D.-K.K., S.Y., G.H.S., J.-I.H., C.R.P., J.Y.S.), Korea University, Seoul 136-705, Republic of Korea; Department of Life Science (J.I.K.), Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea; School of Biological Sciences (K.K.), Seoul National University, Seoul 151-742, Republic of Korea; and Laboratory of Neuronal and Neuroendocrine Differentiation and Communication (H.V.), Inserm U982, University of Rouen, 76821 Mont-St-Aignan, France.
authors: Dong-Kyu
authors: DK
authors: Kim
authors: Seongsik
authors: S
authors: Yun
authors: Gi Hoon
authors: GH
authors: Son
authors: Jong-Ik
authors: JI
authors: Hwang
authors: Cho Rong
authors: CR
authors: Park
authors: Jae Il
authors: JI
authors: Kim
authors: Kyungjin
authors: K
authors: Kim
authors: Hubert
authors: H
authors: Vaudry
authors: Jae Young
authors: JY
authors: Seong
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D030561:Databases, Nucleic Acid; D030562:Databases, Protein; D019143:Evolution, Molecular; D019004:Galanin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020440:Gene Duplication; D057809:HEK293 Cells; D006801:Humans; D059648:Kisspeptins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D009479:Neuropeptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D036361:Peptide Hormones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D044091:Receptor, Galanin, Type 1 / Q000819:agonists / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D044092:Receptor, Galanin, Type 2 / Q000819:agonists* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D044093:Receptor, Galanin, Type 3 / Q000819:agonists* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000074502:Receptors, Kisspeptin-1; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D026801:Synteny; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: C056567:GAL protein, human; C106628:KISS1 protein, human; C118688:KISS1R protein, human; D059648:Kisspeptins; D008024:Ligands; D009479:Neuropeptides; D036361:Peptide Hormones; D020033:Protein Isoforms; D044091:Receptor, Galanin, Type 1; D044092:Receptor, Galanin, Type 2; D044093:Receptor, Galanin, Type 3; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D011994:Recombinant Proteins; C546416:SPX protein, human; D029961:Zebrafish Proteins; D019004:Galanin