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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
.
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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.
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23185286
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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 10−6 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 ß-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. = Non 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 5′ to 3′. 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.
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