Researchers have discovered that snakes have lost the genes responsible for producing ghrelin, commonly known as the hunger hormone, along with the enzyme needed to activate it. This finding provides important insights into how snakes have adapted to their unique feeding behaviors, particularly their ability to survive extended periods without food.
The study examined 112 species across multiple reptile groups, including lizards, turtles, crocodilians, and tuataras. The researchers searched through genetic databases to identify whether the ghrelin gene and its associated enzyme, MBOAT4, were present or absent in these species. Their methodology involved using computational tools to scan genomes for these genes, checking for functional sequences versus degraded or missing genetic material. They also examined neighboring genes to confirm that the absence was genuine rather than an artifact of incomplete genome sequences.
Ghrelin plays a central role in regulating appetite and energy metabolism in most vertebrates. In its unacylated form, ghrelin increases during fasting periods. After an animal eats, the MBOAT4 enzyme converts this inactive form into acylated ghrelin, which then triggers hunger signals and affects how the body processes and stores fat. This dual system helps animals respond appropriately to fed versus fasted states, influencing both immediate feeding behavior and longer-term metabolic processes like fat storage and mobilization.
The results showed that the ghrelin gene has been lost independently in three distinct lineages: all 32 snake species examined, four species of chameleons, and two species of toadhead agamas. Correspondingly, the MBOAT4 enzyme gene was also degraded or absent in these same groups. The researchers determined gene loss by identifying mutations that disrupted the normal genetic sequence, including premature stop codons that would prevent protein production, missing sections of genes, and damaged splice sites that are necessary for proper gene function. They established that genes were considered pseudogenized when disruptive mutations affected more than 30 percent of the genetic sequence.
The researchers propose that losing this hormonal signaling system relates to fundamental changes in how these animals manage energy. Snakes are well known for their extreme feeding ecology, capable of consuming large prey items and then fasting for months or even over a year. During these extended fasting periods, they dramatically reduce their resting metabolic rate to conserve energy. Between meals, snakes minimize metabolic costs, but when they do eat, they undergo substantial physiological changes, including increased gastric acid secretion and a metabolic spike associated with digestion.
This metabolic spike, called the specific dynamic action response, is particularly energy-intensive in ectothermic reptiles compared to warm-blooded mammals and birds. To accommodate large meals and lengthy digestion times, snakes have evolved numerous adaptations in their digestive anatomy and physiology. Previous research has shown that after feeding, Burmese pythons alter the expression of hundreds or thousands of genes related to intestinal structure and metabolism.
The evolutionary loss of ghrelin and MBOAT4 in snakes may represent an adaptation to this feast-or-famine lifestyle. Without the standard ghrelin signaling system that promotes hunger and influences fat metabolism based on feeding status, snakes may have developed alternative regulatory mechanisms better suited to their extreme metabolic fluctuations. This gene loss could be considered adaptive if eliminating these genes provided a selective advantage, or it might be a neutral consequence of other physiological changes that rendered the genes unnecessary.
The findings are particularly notable because ghrelin and MBOAT4 have been found across diverse vertebrate groups, including mammals, birds, amphibians, and fish. Previous studies had detected signs of ghrelin gene degradation in egg-laying mammals called monotremes, likely linked to their loss of a functional stomach. The current study clarifies earlier contradictory findings about ghrelin in turtles, confirming that turtles, along with most lizards and crocodilians, retain functional versions of both genes.
The independent loss of these genes in chameleons and toadhead agamas suggests that similar selective pressures or metabolic adaptations may have occurred in these groups. However, the study primarily focuses on establishing the pattern of gene loss rather than fully explaining the functional consequences. Understanding precisely how snakes regulate appetite and metabolism without ghrelin represents an important area for future investigation, potentially revealing novel hormonal pathways or regulatory mechanisms that compensate for this loss.