Molecular Coevolution of Neuropeptides Gonadotropin-Releasing Hormone and Kisspeptin with their Cognate G Protein-Coupled Receptors

Abstract

The neuropeptides gonadotropin-releasing hormone (GnRH) and kisspeptin (KiSS), and their receptors gonadotropin-releasing hormone receptor (GnRHR) and kisspeptin receptor (KiSSR) play key roles in vertebrate reproduction. Multiple paralogous isoforms of these genes have been identified in various vertebrate species. Two rounds of genome duplication in early vertebrates likely contributed to the generation of these paralogous genes. Genome synteny and phylogenetic analyses in a variety of vertebrate species have provided insights into the evolutionary origin of and relationship between paralogous genes. The paralogous forms of these neuropeptides and their receptors have coevolved to retain high selectivity of the ligand–receptor interaction. These paralogous forms have become subfunctionalized, neofunctionalized, or dysfunctionalized during evolution. This article reviews the evolutionary mechanism of GnRH/GnRHR and KiSS/KiSSR, and the fate of the duplicated paralogs in vertebrates.

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

“…This clade also encompasses the Elopomorphes European eel, the Actinopterygians spotted gar and three sarcopterygian species (Xenopus, bullfrog and coelacanth) (Pasquier et al 2012a). Synteny analysis shows that the four kissr neighboring genomic regions are highly conserved, and when multiple genes are identified in the same species, they are located in different chromosomes , Um et al (2009), Akazome et al (2010), Kim et al (2012), Pasquier et al (2012a,b) and this study). Our phylogenetic and synteny analyses agree with those data suggesting that this gene family might have arisen from a single ancestral gene -and genomic region -through the two successive WGDs (1R and 2R) early in vertebrate evolution, resulting in these four kissr paralogons.…”

“…It seems that the ocurrence of a third WGD event (3R) in the teleost fish lineage (w350 million years ago) had no impact on the number of kissr paralogs in current teleosts, as the potential existence of up to eight kiss receptor genes has not been reported in any species analyzed (Pasquier et al 2014a,b). So far, the common ancestral kissr gene diversified through gene duplication, with subsequent gene losses, to display a large variability of Kiss receptors (and ligands) depending on the species (Akazome et al 2010, Um et al 2010, Kim et al 2012, Pasquier et al 2012a,b, 2014a. In this context, the impact of these events in Gnathostomos (chondrichthyans) and Agnathos (cyclostomes) is still uncertain.…”

“…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.…”

“…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).…”

MOLECULAR EVOLUTION OF GPCRS: GLP1/GLP1 receptors

“…As the SCTR-like receptors and their peptide ligands share similar structural features, they are likely to have emerged through gene/genome duplications from common ancestors. Duplicated receptors and peptides have undergone sequence changes during evolution, leading to diversification of their physiological functions (Acharjee et al 2004, Kim et al 2012. Specific diversification of peptides, i.e.…”