UCSF

Specialization on fruit, or frugivory, is a dietary adaptation that has evolved multiple times in primates and bats. While there are some genes that have been linked to this dietary specialization, the genetic factors, particularly gene regulatory factors, underlying mammalian frugivory are largely unknown. In this work, I utilized a combination of comparative and functional genomics to identify and functionally examine genetic factors for frugivorous adaptation in mammals. First, I used accelerated regions analysis to identify regions of the genome that are highly conserved across mammals but have significantly changed in fruit-eating bats and primates, termed frugivorous accelerated regions (FARs), and tested selected FARs in vitro and in vivo. I found that FARs drive transcriptional activity in luciferase reporter assays and mouse transgenic reporter assays, and we are now examining FAR phenotypes from mouse genomic sequence swapping. Next, I conducted the first combined single-cell RNA- and ATAC-seq on fasted and fed frugivorous and insectivorous bat kidneys and pancreases. We characterized cell composition, gene expression, and gene regulation in these heterogeneous tissues and revealed many novel cellular and molecular traits in frugivorous bats. Importantly, we found frugivorous bats share many traits with human diabetes and demonstrate how our integrative single-cell profilings can be used for therapeutic purposes.