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Ghrelin and MBOAT4 are lost in Serpentes.

Rui Resende Pinto1,2, Raquel Ruivo1, Josefin Stiller3

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|February 3, 2026
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The hunger hormone ghrelin (GHRL) and its activating enzyme MBOAT4 were independently lost in snakes, chameleons, and toadhead agamas. This loss in reptiles may reflect adaptations for lower energy expenditure and prolonged fasting periods.

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Area of Science:

  • Evolutionary biology
  • Comparative genomics
  • Physiological adaptations

Background:

  • Metabolic and energetic homeostasis are crucial for organismal survival and adaptation.
  • Gene network evolution provides insights into physiological changes in different lineages.
  • Ghrelin (GHRL) is a key hormone regulating appetite, food intake, and body weight.

Purpose of the Study:

  • To investigate the evolutionary trajectory of the ghrelin (GHRL) hormonal system in reptiles.
  • To identify specific reptile lineages where GHRL signaling has been lost.
  • To correlate the loss of GHRL with metabolic and physiological adaptations.

Main Methods:

  • Genomic analysis of 112 reptile species across Squamata, Testudines, Crocodilia, and Rhynchocephalia.
  • Identification of GHRL gene presence/absence and MBOAT4 gene integrity.
  • Comparative analysis of gene loss events and physiological traits.

Main Results:

  • Independent loss of the GHRL gene was observed in snakes (32 species), chameleons (4 species), and toadhead agamas (2 species).
  • The gene for the ghrelin-activating enzyme, MBOAT4, is also eroded in these same lineages.
  • The loss of the GHRL/MBOAT4 system correlates with metabolic shifts, including reduced resting energy expenditure.

Conclusions:

  • The ghrelin signaling pathway has been independently lost multiple times in reptiles.
  • This loss is associated with adaptations for reduced energy expenditure and prolonged fasting capabilities.
  • Evolutionary pressures have shaped the energy metabolism and hormonal regulation in these reptile groups.