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

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

JOURNAL=Frontiers in Neuroscience

VOLUME=12

YEAR=2018

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2018.00607

DOI=10.3389/fnins.2018.00607

ISSN=1662-453X

ABSTRACT=<p>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 <italic>GnRH</italic> 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, <italic>Scyliorhinus canicula</italic>, the whale shark, <italic>Rhincodon typus</italic> and the elephant shark <italic>Callorhinchus milii</italic>. In each species, we report the identification of three <italic>GnRH</italic> genes. In catshark and whale shark, phylogenetic and synteny analysis showed that these three genes correspond to <italic>GnRH1, GnRH2</italic>, and <italic>GnRH3</italic>. In both species, <italic>GnRH1</italic> 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 <italic>GnRH1</italic> gene, plus <italic>GnRH2</italic>. 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 <italic>GnRH1, GnRH2</italic>, and <italic>GnRH3</italic> genes are differentially expressed in the catshark brain. <italic>GnRH1</italic> mRNA appeared predominant in the diencephalon while <italic>GnRH2</italic> and <italic>GnRH3</italic> mRNAs seemed to be most abundant in the mesencephalon and telencephalon, respectively. Taken together, our results show that the <italic>GnRH</italic> gene repertoire of the vertebrate ancestor was entirely conserved in the chondrichthyan lineage but that the <italic>GnRH3</italic> gene was probably lost in holocephali. They also suggest that the three <italic>GnRH</italic> neuronal systems previously described in the brain of bony vertebrates are also present in cartilaginous fish.</p>