Abstract
Recent studies have revealed that the hypothalamic hypocretin (Hcrt) neuropeptide system is centrally involved in mammalian REM sleep and that it may have other diverse physiological roles. The aims of this work were to learn when HCRT emerged and to test our previous hypothesis that it was created by a circular permutation of an incretin superfamily gene. We found HCRT in fish and believe the gene arose approximately 650 million years ago, in the early chordate lineage. Our comparison of Hcrts to the most similar members of the incretin peptide superfamily leads us to conclude that HCRTs are indeed incretin paralogs that arose by a genetic circular permutation.
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