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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.

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