| Abstract |
While excessive consumption of glucose- and fructose-sweetened soft drinks is a major risk factor for type 2 diabetes and metabolic syndrome in humans, several nectarivorous bird lin- eages have adapted their metabolism to rely mostly on simple sugars obtained from flower nectar. These lineages are spread around the world and include hummingbirds (Americas), honeyeaters and lorikeets (Australasia), and sunbirds (Africa and Asia). All these nectarivores have evolved distinct phenotypic traits allowing them to rely mostly on nectar as a source of nutrients. However, the genomic underpinnings of these natural adaptations to nectarivory are largely unknown. In order to identify genomic changes underlying metabolic adaptations of nectarivorous birds, we produced new genomic and transcriptomic data, and combining them with publically avail- able data, we ran a number of comprehensive comparative screens. To confirm our theoretical findings, we complemented them with experimental validation. The genome-wide screen for hummingbird-specific gene losses identified the loss of FBP2, a gene encoding a key gluconeogenic enzyme that is normally active in muscles of all tetrapods. Loss of FBP2 occurred around a time where energy-demanding hovering flight is thought to have evolved in hummingbirds. We hypothesized that FBP2 loss could have contributed to the evolution of their metabolic adaptations in muscles. To test this, we downregulated the gene in a bird muscle cell line. Even a partial knockout of FBP2 significantly upregulated glycolysis and mitochondrial respiration in cells. In our experiments, we also show that the latter is likely happening due to the increased number of mitochondria. Together, these results suggest that FBP2 loss contributed to metabolic adaptations that likely enhanced hummingbirds’ ability to immediately process newly ingested sugars thus providing energy for the hovering flight. To study the convergence of adaptations to nectarivory, we ran a number of screens search- ing for convergent and lineage-specific genomic changes. A screen for rapid adaptive evolution identified that a rate-limiting glycolytic enzyme (hexokinase 3) evolved under strong positive se- lection in the stem honeyeaters, potentially underlying similar metabolic changes to what FBP2 loss has introduced in hummingbirds. These results provide a deep insight into the genomic basis of adaptations to high-sugar ‘soft drink-like’ diets in birds. These findings have the potential not only to answer important evolu- tionary questions but also to teach us lessons concerning type 2 diabetes, metabolic syndrome, and obesity in humans. |