Multiple Kisspeptin Receptors in Early Osteichthyans Provide New Insights into the Evolution of This Receptor Family

Jérémy Pasquier,Anne-Gaëlle Lafont,Ching-Fong Chang,Marina Morini,Jonna Tomkiewicz,Guido Van Den Thillart,Sylvie Dufour,Shan-Ru Jeng,Karine Rousseau,Ron Dirks,Hervé Tostivint

doi:10.1371/journal.pone.0048931

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.

Highlights

In 1999, a novel G protein-coupled receptor named GPR54 was cloned from the rat brain [1]
TBLASTN results revealed the presence of three different kisspeptin receptor (Kissr) genes, called Kissr-1, -2, -3, each made of 5 exons and 4 introns (Fig. S1), that constitutes the conserved structure of Kissr genes
Our study provides the first evidence of multiple Kissr paralogs in basal osteichthyans, with the cloning of three Kissr in a basal teleost, the eel, and the prediction of four Kissr in a nonteleost actinopterygian, the spotted gar, and four Kissr in a basal sarcopterygian, the coelacanth

Summary

Introduction

In 1999, a novel G protein-coupled receptor named GPR54 was cloned from the rat brain [1]. GPR54 ligands were later shown to be kisspeptins, previously described as metastasis suppressors, encoded by Kiss gene [2]. A second Kissr gene could be evidenced in some species including zebrafish (Danio rerio) [6], goldfish (Carassius auratus) [7], medaka (Oryzias latipes) [4], and striped bass (Morone saxatilis) [8]. This second paralog is lacking in the genomes of other teleosts, such as fugu (Takifugu niphobles), tetraodon (Tetraodon nigroviridis) and stickleback (Gasterosteus aculeatus). The homology relationships between the various Kissr and the evolutionary events that led to such diversity are still ambiguous

Methods

Results

Conclusion