Sugar assimilation underlying dietary evolution of Neotropical bats
Authors: Camacho Jasmin , Bernal-Rivera Andrea , Peña Valentina , Morales-Sosa Pedro , Robb Sofia , Russell Jonathon , Yi Kexi , Wang Yongfu , Tsuchiya Dai , Murillo-García Oscar E. , Rohner Nicolas 
Published: July 2023

Specializations in animal diets drive selective demands on morphology, anatomy, and physiology. Studying adaptations linked to diet evolution benefits from examining Neotropical bats, a remarkable group with high taxonomic and trophic diversity. In this study, we performed glucose tolerance tests on wild-caught bats, which revealed distinct responses to three sugars present in different foods: trehalose (insects), sucrose, and glucose (fruits and nectar). Insect-eating bats metabolism responded most strongly to trehalose, while bats with nectar and fruit-based diets exhibited a heightened response to glucose and sucrose, reaching blood glucose levels over 600 and 750 mg/dL. To search for signatures of positive selection in sugar assimilation genes we performed genome analysis of 22 focal bat species and 2 outgroup species. We identified selection in the ancestral vespertilionid branch (insect-eaters) for the digestive enzyme trehalase, while sucrase-isomaltase exhibited selection in branches leading to omnivorous and nectar diets. Unexpectedly, the insect-eating lineageMyotisexhibited sucrase-isomaltase selection, potentially explaining their heightened sucrose assimilation. Furthermore, the genes encoding for glucose transporters,Slc2a3andSlc2a2,showed selection in nectar and blood feeding bats, with analyses of predicted protein structures supporting modified activity. By examining cellular features of the small intestine, we discovered that dietary sugar proportion strongly impacted numerous digestive traits, providing valuable insight into the physiological implications of the identified molecular adaptations. To elucidate this further, we used HCR RNA-FISH to perform single moleculeex vivogene expression analysis of enterocyte response to a glucose meal in three focal species. We observed unusually high activity in the glucose transporterSlc2a2during the fasted state of nectar bats that did not change upon feeding. Comparatively, nectar bats exhibited an enhanced capacity for intestinal absorption of dietary sugar primarily throughSlc2a2, while fruit bats relied on increasing levels ofSlc5a1. Overall, this study highlights the intricate interplay between molecular, morphological, and physiological aspects of diet evolution and provides new insights into our understanding of dietary diversification and sugar assimilation mechanisms in mammals.

Graphical Abstract

Highlights

Sugar assimilation differences emphasize metabolic adaptations to diet

Glucose tolerance tests provide a quick and practical assessment of dietary ecology

Bat genomes exhibit positive selection on digestive enzymes and glucose transporters

Structural comparisons of proteins suggest altered activity of glucose transporters

Glucose absorption differences can be explained by gut anatomy

Intestinal villus diversity and novel microanatomy in bats

Extreme blood glucose (above 600 and 750 mg/dL) coincides with constitutive expression of apicalSlc2a2

The regulation of apicalSlc2a2highlights differences in blood glucose levels