Ghrelin and MBOAT4 are lost in Serpentes

Abstract Exploring the evolution of gene networks associated with metabolic/energetic homeostasis can yield key insights into the adaptive landscapes governing the physiology of extant lineages. Here, we investigate a key hormonal module of energy metabolism in reptiles. Ghrelin (GHRL), also known as the ‘hunger hormone’, is a multifunctional gastric peptide, involved in appetite, food intake and body weight regulation. We examined the genomes of 112 species comprising members of the Squamata, Testudines, Crocodilia and Rhynchocephalia and provided ample evidence that GHRL was independently lost in snakes (32 species), chameleons (four species) and toadhead agamas (two species). In accordance, the enzyme responsible for ghrelin acylation and essential for its activity, MBOAT4 (membrane bound O-acyltransferase domain containing 4), is also eroded in these lineages. We suggest that the loss of this hormonal signalling system parallels critical modifications in energy metabolism, such as lower energy expenditure during rest, possibly linked with their unique ability to undergo large periods of fasting.