The emergence and loss of gonadotropin-releasing hormone in protostomes: orthology, phylogeny, structure, and function.

Gonadotropin-releasing hormone (GNRH) is a neuropeptide critical for reproductive activation and maintenance in vertebrates. The recent elucidation of molluscan GNRH-like sequences led to several important questions regarding the evolution of the GNRH family. For instance, are molluscan and chordate GNRHs true orthologs? Has GNRH been retained in most protostomian lineages? What was the function of the ancestral GNRH? The goal of this review is to provide a critical analysis of GNRH evolution based on data available from the known forms of protostomian GNRH. Judging from the orthology between chordate and protostomian GNRH receptors, conservation of several structural motifs on the GNRH peptide, and exon/intron arrangement conserved between protostomian and chordate GNRH genomic sequences, we conclude that chordate and protostomian GNRHs likely share a common ancestor. Based on our analysis of phylogenetic distribution, we also hypothesize that GNRH may have been lost in the ecdysozoan lineage but preserved in lophotrochozoans. Lastly, we propose that the ancestral function of GNRH is to serve as a general neural regulator, and its considerable specialization in reproduction seen in chordates is a consequence of neofunctionalization following gene duplication.