Neurobiology and Genetics

Receptor deorphanization in an echinoderm reveals kisspeptin evolution and relationship with SALMFamide neuropeptides


During puberty our bodies undergo changes whereby a child's body matures into an adult body capable of sexual reproduction. In some people, however, the onset of puberty is delayed and genetic analysis of this condition has provided insights into the hormonal mechanisms that control sexual maturation. Thus, in 2003 it was discovered that onset of puberty is triggered by the release of a hormone in the brain (a neurohormone) known as kisspeptin, which then exerts its effects by binding to a protein known as the kisspeptin receptor. But when did kisspeptin and its receptor originate in the evolutionary history of life on earth?

To address this question, the genomes of different types of invertebrate animals were analysed to search for genes encoding proteins related to the human kisspeptin receptor. This revealed the presence of genes encoding kisspeptin-type receptors in several different types of invertebrates, including molluscs (e.g. snails), annelids (e.g. earthworms) and echinoderms (e.g. starfish). Based on this finding, the researchers concluded that kisspeptin and its receptor must have originated at least half-a-billion years ago in a common ancestor of the Bilateria - animals that exhibit bilateral symmetry during their life-cycle, which include most animals on earth. What’s more the researchers discovered that, unlike humans that have just one kisspeptin receptor gene, some animals such as starfish have lots of genes encoding kisspeptin-type receptors, whilst others animals such as insects do not have any because of gene loss during their evolutionary history. To further investigate the functional significance of the occurrence of an expanded family of genes encoding kisspeptin-type receptors in starfish, the common European species Asterias rubens was selected as an experimental model. Remarkably, this species has eleven genes encoding proteins related to the human kisspeptin receptor and four genes encoding nineteen kisspeptin-like molecules that bind to and activate one or more of the eleven kisspeptin-type receptors.

The surprising discovery of such a complex chemical signalling system in starfish has provided new insights into the evolutionary history of kisspeptin. The findings indicate that the common ancestor of bilaterian animals would have had at least two types of kisspeptins, one of which appears to have been lost in the vertebrate lineage that includes humans. Furthermore, starfish and their kind have uniquely evolved kisspeptin-related molecules known as SALMFamides, neurohormones that were first discovered in starfish over thirty years ago, long before the discovery of kisspeptin as a puberty hormone in humans.

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Journal: BMC Biology
Autoren:  Escudero Castelan, N., Semmens, D. C., Guerra, L. A. Y., Zandawala, M., Dos Reis, M., Slade, S. E., Scrivens, J. H., Zampronio, C. G., Jones, A. M., Mirabeau, O., and Elphick, M. R.