Ancient origins of metazoan gonadotropin-releasing hormone and their receptors revealed by phylogenomic analyses

• Deuterostome GnRH and protostome GnRH-like peptide hormones are orthologs.
• GnRH receptors and their relatives are part of a large class of ancient neuromodulatory GPCRs.
• GnRH receptors are related to vasopressin, neuropeptide S and GPCR 150, which are restricted to bilaterians.
• The relationships of the receptors recapitulate the phylogeny of their peptide hormone ligands.

The discovery of genes related to gonadotropin-releasing hormones (GnRH) and their receptors from diverse species has driven important advances in comparative endocrinology. However, our view of the evolutionary histories and nomenclature of these gene families has become inconsistent as several different iterations of GnRH and receptor relationships have been proposed. Whole genome sequence data are now available for most of the major lineages of animals, and an exhaustive view of the phylogenies of GnRH and their receptors is now possible. In this paper, we leverage data from publically available whole genome sequences to present a new phylogenomic analysis of GnRH and GnRH receptors and the distant relatives of each across metazoan phylogeny. Our approach utilizes a phylogenomics pipeline that searches data from 36 whole genome sequences and conducts phylogenetic analyses of gene trees. We provide a comprehensive analysis of the major groupings of GnRH peptides, related hormones and their receptors and provide some suggestions for a new nomenclature. Our study provides a framework for understanding the functional diversification of this family of neuromodulatory peptides and their receptors.

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