Characterization of Gonadotropin-Releasing Hormone (GnRH) Genes From Cartilaginous Fish: Evolutionary Perspectives.

Anne-Laure Gaillard,Boon-Hui Tay,Byrappa Venkatesh,Sylvie Dufour,Daniela I Pérez Sirkin,Hervé Tostivint,Anne-Gaëlle Lafont,Paula G Vissio,Sylvie Mazan,Céline De Flori

doi:10.3389/fnins.2018.00607

Abstract

The neuropeptide gonadotropin-releasing hormone (GnRH) plays an important role in the control of reproductive functions. Vertebrates possess multiple GnRH forms that are classified into three main groups, namely GnRH1, GnRH2, and GnRH3. In order to gain more insights into the GnRH gene family in vertebrates, we sought to identify which paralogs of this family are present in cartilaginous fish. For this purpose, we searched the genomes and/or transcriptomes of three representative species of this group, the small-spotted catshark, Scyliorhinus canicula, the whale shark, Rhincodon typus and the elephant shark Callorhinchus milii. In each species, we report the identification of three GnRH genes. In catshark and whale shark, phylogenetic and synteny analysis showed that these three genes correspond to GnRH1, GnRH2, and GnRH3. In both species, GnRH1 was found to encode a novel form of GnRH whose primary structure was determined as follows: QHWSFDLRPG. In elephant shark, the three genes correspond to GnRH1a and GnRH1b, two copies of the GnRH1 gene, plus GnRH2. 3D structure prediction of the chondrichthyan GnRH-associated peptides (GAPs) revealed that catshark GAP1, GAP2, and elephant shark GAP2 peptides exhibit a helix-loop-helix (HLH) structure. This structure observed for many osteichthyan GAP1 and GAP2, may convey GAP biological activity. This HLH structure could not be observed for elephant shark GAP1a and GAP1b. As for all other GAP3 described so far, no typical 3D HLH structure was observed for catshark nor whale shark GAP3. RT-PCR analysis revealed that GnRH1, GnRH2, and GnRH3 genes are differentially expressed in the catshark brain. GnRH1 mRNA appeared predominant in the diencephalon while GnRH2 and GnRH3 mRNAs seemed to be most abundant in the mesencephalon and telencephalon, respectively. Taken together, our results show that the GnRH gene repertoire of the vertebrate ancestor was entirely conserved in the chondrichthyan lineage but that the GnRH3 gene was probably lost in holocephali. They also suggest that the three GnRH neuronal systems previously described in the brain of bony vertebrates are also present in cartilaginous fish.

Highlights

Gonadotropin-releasing hormone (GnRH) is the major hypothalamic neurohormone regulating reproduction in vertebrates (Kah et al, 2007; Okubo and Nagahama, 2008)
The GnRH2 cDNA consists of a 99 bp 5 untranslated region (UTR), a 275 bp 3 UTR, with the consensus polyadenylation signal; the 258 bp open reading frame (ORF) encoding a peptide of 86 aa which comprises a 24 aa putative signal peptide, the decapeptide GnRH2, the 3 aa proteolytic cleavage site GKR, and the 49 aa GnRH-associated peptides (GAPs) (Figure 1B)
The GnRH2 cDNA consists of a 14 bp 5 UTR, a 293 bp 3 UTR, and a consensus polyadenylation signal; the 258 bp ORF encoding a peptide of 86 aa which comprises a 24 aa putative signal peptide, the decapeptide GnRH2, the 3 aa proteolytic cleavage site GKR, and the 49 aa GAP (Supplementary Data Sheet S7)

Summary

Introduction

Gonadotropin-releasing hormone (GnRH) is the major hypothalamic neurohormone regulating reproduction in vertebrates (Kah et al, 2007; Okubo and Nagahama, 2008). GnRH1 is seen as the authentic GnRH that stimulates gonadotropin release (Kah et al, 2007; Okubo and Nagahama, 2008). In contrast to GnRH1 which primarily acts as a neurohormone, GnRH2 and GnRH3 are generally viewed as neuromodulatory factors (Okubo and Nagahama, 2008). They have both been implicated in the control of reproductive behavior, their functions are far from being fully understood (Okubo and Nagahama, 2008)

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Conclusion