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Evolution of Orexin Neuropeptide System: Structure and Function.

Shingo Soya1, Takeshi Sakurai1

  • 1Faculty of Medicine/International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan.

Frontiers in Neuroscience
|August 6, 2020
PubMed
Summary

Orexins are brain peptides regulating feeding and sleep. This system, found in vertebrates, evolved to support wakefulness and motivated behaviors.

Keywords:
OX1ROX2Rhypothalamusneuropeptideorexinvertebrate

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Area of Science:

  • Neuroscience
  • Endocrinology
  • Evolutionary Biology

Background:

  • Orexins are hypothalamic neuropeptides acting as ligands for G-protein-coupled receptors (GPCRs).
  • They regulate critical physiological functions including feeding behavior, autonomic functions, and sleep-wake states.
  • Two orexin peptides, orexin A and orexin B, are derived from a common precursor, prepro-orexin.

Purpose of the Study:

  • To explore the evolutionary conservation and phylogenetic origins of the orexin system.
  • To understand the structural evolution of orexin receptors (OX1R and OX2R).
  • To investigate the role of orexins in motivated behaviors and wakefulness across species.

Main Methods:

  • Comparative genomics analysis of orexin and orexin receptor genes across vertebrate species.
  • Phylogenetic reconstruction to infer evolutionary relationships.
  • Review of existing literature on orexin system function and localization.

Main Results:

  • Orexin and its receptor system are conserved throughout vertebrate evolution, with OX2R appearing as the ancestral receptor type.
  • OX1R likely evolved during early mammalian radiation, suggesting a specialized role in mammals.
  • Orexin-producing neurons are primarily in the lateral hypothalamic area (LHA) and are linked to motivated behaviors and wakefulness.

Conclusions:

  • The orexin system's conservation highlights its fundamental role in vertebrate physiology.
  • The evolution of OX1R in mammals may reflect adaptations for complex behaviors.
  • The orexin system appears to have evolved to support active, purposeful behaviors associated with wakefulness.