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PLoS One
2012 Jan 01;711:e48931. doi: 10.1371/journal.pone.0048931.
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Multiple kisspeptin receptors in early osteichthyans provide new insights into the evolution of this receptor family.
Pasquier J
,
Lafont AG
,
Jeng SR
,
Morini M
,
Dirks R
,
van den Thillart G
,
Tomkiewicz J
,
Tostivint H
,
Chang CF
,
Rousseau K
,
Dufour S
.
Abstract
Deorphanization of GPR54 receptor a decade ago led to the characterization of the kisspeptin receptor (Kissr) in mammals and the discovery of its major role in the brain control of reproduction. While a single gene encodes for Kissr in eutherian mammals including human, other vertebrates present a variable number of Kissr genes, from none in birds, one or two in teleosts, to three in an amphibian, xenopus. In order to get more insight into the evolution of Kissr gene family, we investigated the presence of Kissr in osteichthyans of key-phylogenetical positions: the coelacanth, a representative of early sarcopterygians, the spotted gar, a non-teleost actinopterygian, and the European eel, a member of an early group of teleosts (elopomorphs). We report the occurrence of three Kissr for the first time in a teleost, the eel. As measured by quantitative RT-PCR, the three eel Kissr were differentially expressed in the brain-pituitary-gonadal axis, and differentially regulated in experimentally matured eels, as compared to prepubertal controls. Subfunctionalisation, as shown by these differences in tissue distribution and regulation, may have represented significant evolutionary constraints for the conservation of multiple Kissr paralogs in this species. Furthermore, we identified four Kissr in both coelacanth and spotted gar genomes, providing the first evidence for the presence of four Kissr in vertebrates. Phylogenetic and syntenic analyses supported the existence of four Kissr paralogs in osteichthyans and allowed to propose a clarified nomenclature of Kissr (Kissr-1 to -4) based on these paralogs. Syntenic analysis suggested that the four Kissr paralogs arose through the two rounds of whole genome duplication (1R and 2R) in early vertebrates, followed by multiple gene loss events in the actinopterygian and sarcopterygian lineages. Due to gene loss there was no impact of the teleost-specific whole genome duplication (3R) on the number of Kissr paralogs in current teleosts.
Figure 2. Consensus phylogenetic tree of the vertebrate kisspeptin receptors (Kissr).This phylogenetic tree was constructed based on the amino-acid sequences of Kissr (for the references of each sequence see Table S2) using the Maximum Likelihood method with 1,000 bootstrap replicates. The number shown at each branch node indicates the bootstrap value (%); only values and branching above 70% are indicated. The tree was rooted using the two sequences of the hemichordata acorn worm GPR54-1 and GPR54-2 and the two sequences of echinodermata purple sea urchin Kissr_short and Kissr_long. The European eel Kissr and predicted coelacanth and spotted gar Kissr are coloured in red, blue and green, respectively.
Figure 3. Conserved genomic synteny of osteichthyan Kissr.Genomic synteny maps comparing the orthologs of Kissr-1 (A), Kissr-2 (B), Kissr-3 (C), Kissr-4 (D) loci and their neighbouring genes. Analyses were performed on the genomes of human (Homo sapiens), platypus (Ornithorhynchus anatinus), lizard (Anolis carolinensis), chicken (Gallus gallus), xenopus (Xenopus (Silurana) tropicalis), coelacanth (Latimeria chalumnae), spotted gar (Lepisosteus oculatus), zebrafish (Danio rerio), medaka (Oryzias latipes), stickleback (Gasterosteus aculeatus), tetraodon (Tetraodon nigroviridis) and European eel (Anguilla anguilla). This map was established using the PhyloView of Genomicus v67.01 web site, manual annotation of European eel genome using CLC DNA Workbench 6 software and the gene annotation of the coelacanth and spotted gar genomic databases (see section 2). Kissr genes are named according to our proposed nomenclature (Kissr-1 to Kissr-4). The other genes are named after their human orthologs according to Human Genome Naming Consortium (HGNC). Orthologs of each gene are shown in the same color. Each of the eight conserved gene families is identified by an exponent number. The direction of arrows indicates the gene orientation, with the position of the gene (in 10â6 base pairs) indicated below. The full gene names and detailed genomic locations are given in Table S3.
Figure 4. Proposed origin of osteichthyans Kissr loci based on human and spotted gar Kissr tetra-paralogons.The paralogous genes of each of the eight identified families delineate four tetra-paralogons in both human and spotted gar. This suggests a common origin of the four loci before the two whole genome duplication rounds (1R and 2R) occurred in the early vertebrate history.
Figure 5. Current status and proposed evolutionary history of Kissr family.This representation is based on the phylogenetic and synteny analyses. The names of the main phyla are given on the corresponding branches. The names of the current representative species of each phylum are given at the end of the final branches, together with the symbol of the Kissr gene they possess. This hypothesis assumes the presence of the four Kissr paralogs in the osteichthyan lineage resulting from the two rounds of vertebrate whole genome duplication. Multiple subsequent Kissr gene loss events are indicated in the actinopterygian and sarcopterygian lineages.
Figure 6. Tissue distribution of the expression of the three eel Kissr mRNAs.Olfactory bulbs (OB), telencephalon (Tel), di-/mes-encephalon (Di/Mes), cerebellum (Cb), medulla oblongata (MO), pituitary, ovary, testis, muscle, eye, liver, adipose tissue (Fat), kidney, intestine and spleen. The relative expression of each Kissr mRNA was normalised to the amount of total RNA. Each bar represents mean ± SEM from 8 individuals.
Figure 7. Regulations of the three eel Kissr expressions during experimental maturation.The relative expression of each Kissr mRNA was normalised to Ã-actin mRNA. Each bar represents mean ± SEM from 7 control and 9 matured female eels. Significant difference between control and matured groups: *P<0.05, **P<0.01 and *** P<0.001 (Student's t test). N.D.â=âNon detectable.
Figure 1. Molecular cloning of eel Kissr-1 and Kissr-3_v1.Nucleotide and deduced amino-acid sequence of the cDNA encoding the eel Kissr-1 (A) and Kissr-3_v1 (B). Nucleotides (top) are numbered from 5â² to 3â². The amino-acid residues (bottom) are numbered beginning with the first methionine residue in the ORF. The asterisk (*) indicates the stop codon. The predicted seven transmembrane domains (TMD) are underlined and the cysteines involved in a disulphide bridge are shaded in grey.
Abascal,
ProtTest: selection of best-fit models of protein evolution.
2005, Pubmed
Abascal,
ProtTest: selection of best-fit models of protein evolution.
2005,
Pubmed
Akazome,
Functional and evolutionary insights into vertebrate kisspeptin systems from studies of fish brain.
2010,
Pubmed
Amores,
Zebrafish hox clusters and vertebrate genome evolution.
1998,
Pubmed
Amores,
Genome evolution and meiotic maps by massively parallel DNA sequencing: spotted gar, an outgroup for the teleost genome duplication.
2011,
Pubmed
Aroua,
Development of real-time RT-PCR assays for eel gonadotropins and their application to the comparison of in vivo and in vitro effects of sex steroids.
2007,
Pubmed
Biran,
Molecular identification and functional characterization of the kisspeptin/kisspeptin receptor system in lower vertebrates.
2008,
Pubmed
,
Xenbase
Castellano,
Expression of KiSS-1 in rat ovary: putative local regulator of ovulation?
2006,
Pubmed
Dehal,
Two rounds of whole genome duplication in the ancestral vertebrate.
2005,
Pubmed
Dufour,
Differential distribution and response to experimental sexual maturation of two forms of brain gonadotropin-releasing hormone (GnRH) in the European eel, Anguilla anguilla.
1993,
Pubmed
Dufour,
Neuroendocrine control by dopamine of teleost reproduction.
2010,
Pubmed
Dufour,
Positive feedback control by the gonads on gonadotropin (GTH) and gonadoliberin (GnRH) levels in experimentally matured female silver eels,Anguilla anguilla.
1989,
Pubmed
Filby,
The kisspeptin/gonadotropin-releasing hormone pathway and molecular signaling of puberty in fish.
2008,
Pubmed
Funes,
The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system.
2003,
Pubmed
García-Galiano,
Kisspeptin signaling is indispensable for neurokinin B, but not glutamate, stimulation of gonadotropin secretion in mice.
2012,
Pubmed
Gaytán,
KiSS-1 in the mammalian ovary: distribution of kisspeptin in human and marmoset and alterations in KiSS-1 mRNA levels in a rat model of ovulatory dysfunction.
2009,
Pubmed
Henkel,
Primitive duplicate Hox clusters in the European eel's genome.
2012,
Pubmed
Jeng,
Differential regulation of the expression of cytochrome P450 aromatase, estrogen and androgen receptor subtypes in the brain-pituitary-ovarian axis of the Japanese eel (Anguilla japonica) reveals steroid dependent and independent mechanisms.
2012,
Pubmed
Kanda,
Identification of KiSS-1 product kisspeptin and steroid-sensitive sexually dimorphic kisspeptin neurons in medaka (oryzias latipes).
2008,
Pubmed
Kanda,
Steroid sensitive kiss2 neurones in the goldfish: evolutionary insights into the duplicate kisspeptin gene-expressing neurones.
2012,
Pubmed
Kim,
Molecular Coevolution of Neuropeptides Gonadotropin-Releasing Hormone and Kisspeptin with their Cognate G Protein-Coupled Receptors.
2012,
Pubmed
Kotani,
The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54.
2001,
Pubmed
Kuraku,
Timing of genome duplications relative to the origin of the vertebrates: did cyclostomes diverge before or after?
2009,
Pubmed
Kuraku,
Insights into cyclostome phylogenomics: pre-2R or post-2R.
2008,
Pubmed
Lee,
Molecular evolution of multiple forms of kisspeptins and GPR54 receptors in vertebrates.
2009,
Pubmed
,
Xenbase
Lee,
Discovery of a receptor related to the galanin receptors.
1999,
Pubmed
Lehman,
Minireview: kisspeptin/neurokinin B/dynorphin (KNDy) cells of the arcuate nucleus: a central node in the control of gonadotropin-releasing hormone secretion.
2010,
Pubmed
Li,
Structural and functional multiplicity of the kisspeptin/GPR54 system in goldfish (Carassius auratus).
2009,
Pubmed
Martinez-Chavez,
GPR54 and rGnRH I gene expression during the onset of puberty in Nile tilapia.
2008,
Pubmed
Mechaly,
Identification of two isoforms of the Kisspeptin-1 receptor (kiss1r) generated by alternative splicing in a modern teleost, the Senegalese sole (Solea senegalensis).
2009,
Pubmed
Mohamed,
Developmental expression of the G protein-coupled receptor 54 and three GnRH mRNAs in the teleost fish cobia.
2007,
Pubmed
Montero,
Differential regulation of the two forms of gonadotropin-releasing hormone (mGnRH and cGnRH-II) by sex steroids in the European female silver eel (Anguilla anguilla).
1995,
Pubmed
Muffato,
Genomicus: a database and a browser to study gene synteny in modern and ancestral genomes.
2010,
Pubmed
Muir,
AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1.
2001,
Pubmed
Nakatani,
Reconstruction of the vertebrate ancestral genome reveals dynamic genome reorganization in early vertebrates.
2007,
Pubmed
Navarro,
Developmental and hormonally regulated messenger ribonucleic acid expression of KiSS-1 and its putative receptor, GPR54, in rat hypothalamus and potent luteinizing hormone-releasing activity of KiSS-1 peptide.
2004,
Pubmed
Nocillado,
Temporal expression of G-protein-coupled receptor 54 (GPR54), gonadotropin-releasing hormones (GnRH), and dopamine receptor D2 (drd2) in pubertal female grey mullet, Mugil cephalus.
2007,
Pubmed
Onuma,
Duplicated Kiss1 receptor genes in zebrafish: distinct gene expression patterns, different ligand selectivity, and a novel nuclear isoform with transactivating activity.
2012,
Pubmed
Parhar,
GnRH and gpcr: laser-captured single cell gene profiling.
2005,
Pubmed
Pasqualini,
Two distinct dopamine D2 receptor genes in the European eel: molecular characterization, tissue-specific transcription, and regulation by sex steroids.
2009,
Pubmed
Pasquier,
First evidence for a direct inhibitory effect of kisspeptins on LH expression in the eel, Anguilla anguilla.
2011,
Pubmed
Putnam,
The amphioxus genome and the evolution of the chordate karyotype.
2008,
Pubmed
Roa,
Kisspeptins in reproductive biology: consensus knowledge and recent developments.
2011,
Pubmed
Schmitz,
Differential regulation of luteinizing hormone and follicle-stimulating hormone expression during ovarian development and under sexual steroid feedback in the European eel.
2005,
Pubmed
Sébert,
Melatonin activates brain dopaminergic systems in the eel with an inhibitory impact on reproductive function.
2008,
Pubmed
Servili,
Organization of two independent kisspeptin systems derived from evolutionary-ancient kiss genes in the brain of zebrafish.
2011,
Pubmed
Shahab,
Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates.
2005,
Pubmed
Shahjahan,
Elevation of Kiss2 and its receptor gene expression in the brain and pituitary of grass puffer during the spawning season.
2010,
Pubmed
Stamatakis,
Efficient computation of the phylogenetic likelihood function on multi-gene alignments and multi-core architectures.
2008,
Pubmed
Tena-Sempere,
Comparative insights of the kisspeptin/kisspeptin receptor system: lessons from non-mammalian vertebrates.
2012,
Pubmed
Thompson,
CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice.
1994,
Pubmed
Um,
Molecular coevolution of kisspeptins and their receptors from fish to mammals.
2010,
Pubmed
,
Xenbase
Weltzien,
Brain expression of tyrosine hydroxylase and its regulation by steroid hormones in the European eel quantified by real-time PCR.
2005,
Pubmed
Zmora,
Differential and gonad stage-dependent roles of kisspeptin1 and kisspeptin2 in reproduction in the modern teleosts, morone species.
2012,
Pubmed
