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

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.

Differential activation of kiss receptors by Kiss1 and Kiss2 peptides in the sea bass

“…All in all, advances in genome sequencing and comparative genomics in several groups occupying relevant phylogenetic positions have led to the identification of four kissr and three kiss genes in the coelacanth (Sarcopterygian), while in teleosts at least one kiss and kissr is known to be present in all the species investigated to date. Nevertheless, a second gene for kisspeptin and its receptor has been observed in the genomes of other fish species (Biran et al 2008, Akazome et al 2010, Oakley et al 2010, Um et al 2010, Zohar et al 2010, Kim et al 2012, Pasquier et al 2012a,b, Tena-Sempere et al 2012. So far, the occurrence of three kissr and two kiss paralogous genes has been reported in an early group of teleosts, the Elopomorphs (European eel, Anguilla anguilla) (Pasquier et al 2012a,b).…”

“…In the spotted gar, Lepisosteus oculatus (Actinopterygian, Ginglymode), four kissr and two kiss have been identified, while four kiss but no kissr have been characterized in the elephant shark, Callorhinchus milii (Chondrichtyan) (Pasquier et al 2012a,b). Concerning cyclostomes, two kiss and one kissr genes have been identified in the sea lamprey (Petromyzon marinus) (Felip et al 2009, Pasquier et al 2012a. Furthermore, two forms of kiss receptor-like genes have been q 2015 Society for Reproduction and Fertility…”

“…Soon after the Kiss/Gpr54 system had been demonstrated to play a role in the control of reproduction in mammals (Funes et al 2003, de Roux et al 2003, Seminara et al 2003, Pinilla et al 2012, further investigation was initiated in several vertebrate species, leading to the identification of multiple kiss and gpr54 paralogous genes in early osteichthyans (Biran et al 2008, Felip et al 2009, Akazome et al 2010, Oakley et al 2010, Um et al 2010, Zohar et al 2010, Kim et al 2012, Pasquier et al 2012a,b, 2014a,b, Tena-Sempere et al 2012. To date, a single ligand (Kiss) and receptor (Gpr54 or Kissr) have been demonstrated to exist in placental mammals (human, opossum) and reptiles, while mammalian monotrems (platypus) possess two forms of Kiss and Kissr genes.…”

Molecular approaches related to the European eel (Anguilla anguilla) reproductive process

“…Furthermore, according to the phylogenetic analysis, each nuclear steroid sequence is clustered at the base of the teleost clades (Chapter 2; Lafont et al, in press). This is consistent with the basal position of elopomorphs in the phylogeny of teleosts, which was also observed in our previous phylogeny analyses of various gene families (Morini et al, 2015a;Pasquier et al, 2011Pasquier et al, , 2012. The presence of two ESR2 and PR in the eel, compared to a single ESR2 and PR in non-teleost actinopterygian and sarcopterygian species, strengthens the current hypothesis that these nuclear receptors are likely to be the result of the teleost 3R (Bardet et al, 2002;Hawkins et al, 2000).…”

“…The neuropeptide gonadotropin-releasing hormone (GnRH), involved in regulating vertebrate reproduction, is released and triggers the release of gonadotropins by the pituitary gland. The protein Kisspeptin seems to play an important role in the onset of puberty, by activating the release of GnRH in vertebrates, including matured eels (Pasquier et al, 2012). Kisspeptin may also act directly on the pituitary through an inhibitory effect on LHβ expression (Pasquier, 2011).…”