Evolution of GnRH ligand precursors and GnRH receptors in protochordate and vertebrate species.

Primary structure relationships between GnRH precursors or GnRH receptors have received significant attention recently due to rapid DNA sequence determination of gene fragments and cDNAs from diverse species. Concepts concerning the evolutionary history of the GnRH system and its function in mammals, including humans, are likely to be modified as more complete sequence information becomes available. Current evidence suggests occurrence of fewer GnRH ligand and GnRH receptor genes in mammals compared to protochordates, fish and amphibians. Whilst several sequence-related GnRH decapeptide precursors and 2 or 3 separate GnRH receptors are encoded within the genomes of protochordates, fish and amphibians, only two types of GnRH (GnRH-I and GnRH-II) and two GnRH receptors occur in mammals. In addition, fish and mammalian genomes both retain inactive remnants of GnRH ligand or GnRH receptor genes. The number of distinct GnRH receptor genes in teleosts (at least five complete genes in pufferfish and three in zebrafish) partly reflects whole genome duplication during the evolution of this order of animals. Three GnRH receptor genes occur in certain frog species, consistent with the occurrence of up to three types of prepro-GnRH in amphibians. In contrast, only one functional GnRH receptor gene (the type I GnRH receptor) has been identified in humans and chimpanzees and a gene encoding a second receptor, homologous to a functional monkey receptor (the type II GnRH receptor), is either partially or completely silenced in a range of mammalian species (human, chimpanzee, sheep, cow, rat, and mouse). Further work is required to determine the significance of species-specific differences in the GnRH system to reproductive biology. For instance, recent data show that even species as closely related as humans and chimpanzees exhibit important organisational changes in the genes comprising the GnRH system.