The unexpected loss of the "hunger hormone" ghrelin in true passerines: A game changer in migration physiology

Migratory birds must accumulate large amounts of fat prior to migration to sustain long flights. In passerines, the small body size limits the amount of energy stores that can be transported and therefore birds undergo cycles of extreme fattening and rapid exhaustion of reserves. Research on these physiological adaptations was rattled by the discovery that birds have lost the main vertebrate regulator of fat deposition, leptin. Recent studies have thus focused on ghrelin, known as the "hunger hormone", a peptide secreted by the gastrointestinal tract to regulate food intake, body mass, and other important functions in vertebrates. Studies on domestic species showed that in birds ghrelin has effects opposite to those described in mammals, such as inhibiting instead of promoting food intake. Furthermore, a series of recent studies have shown that ghrelin administration influences migratory behaviour in passerine birds, suggesting an important role of this hormone in bird migration. However, using comparative genomic analyses we show that ghrelin has been lost in the largest avian taxon Eupasseres, after the basic split from Acanthisitti about 50 million years ago. Eupasserines, also known as True passerines, include all but two of the ca. 10,000 known passerine species. We further found that the ghrelin receptor (growth hormone secretagogue receptor, GHS-R) is still conserved in passerine birds, as indicated by sites under purifying selection and in line with the effects of ghrelin administration. Thus, ghrelin adds to a list of hormones highly conserved in vertebrates that have lost their main functions in specific taxa. The maintenance of a functional receptor system, however, suggests that in eupasserine birds another ligand has replaced ghrelin, perhaps to bypass the feedback system that would hinder large pre-migratory accumulation of subcutaneous fat.