Structural and functional evolution of gonadotropin-releasing hormone in vertebrates.

The neuropeptide gonadotropin-releasing hormone (GnRH) has a central role in the neural control of vertebrate reproduction. This review describes an overview of what is currently known about GnRH in vertebrates in the context of its structural and functional evolution. A large body of evidence has demonstrated the existence of three paralogous genes for GnRH (GnRH1, GnRH2 and GnRH3) in the vertebrate lineage. They are most probably the products of whole-genome duplications that occurred early in vertebrate evolution. Although GnRH3 has been identified only in teleosts, comparative genomic analyses indicated that GnRH3 has not arisen from a teleost-specific genome duplication, but has been derived from an earlier genome duplication in an ancestral vertebrate, followed by its loss in the tetrapod lineage. A loss of other paralogous genes has also occurred independently in different vertebrate lineages, leading to species-specific differences in the organization of the GnRH system. In addition to the GnRH3 gene, the GnRH2 gene has been deleted or silenced in certain mammalian species, while some teleosts seem to have lost the GnRH1 or GnRH3 gene. The duplicated GnRH genes have undergone subfunctionalization during the evolution of vertebrates; GnRH1 has become the major stimulator of gonadotropins and probably other pituitary hormones as well, whereas GnRH2 and GnRH3 would have functioned as neuromodulators, affecting reproductive behaviour. Conversely, in cases where a paralogous gene for GnRH has been lost, one of the remaining paralogues appears to have adopted its role.