Gene Expression Profiling in the Hibernating Primate, Cheirogaleus Medius

Hibernation is a complex physiological response that some mammalian species employ to evade energetic demands. Previous work in mammalian hibernators suggests that hibernation is activated not by a set of genes unique to hibernators, but by differential expression of genes that are present in all mammals. This question of universal genetic mechanisms requires further investigation and can only be tested through additional investigations of phylogenetically dispersed species. To explore this question, we use RNA-Seq to investigate gene expression dynamics as they relate to the varying physiological states experienced throughout the year in a group of primate hibernators—Madagascar’s dwarf lemurs (genus Cheirogaleus). In a novel experimental approach, we use longitudinal sampling of biological tissues as a method for capturing gene expression profiles from the same individuals throughout their annual hibernation cycle. We identify 90 candidate genes that have variable expression patterns when comparing two active states (Active 1 and Active 2) with a torpor state. These include genes that are involved in metabolic pathways, feeding behavior, and circadian rhythms, as might be expected to correlate with seasonal physiological state changes. The identified genes appear to be critical for maintaining the health of an animal that undergoes prolonged periods of metabolic depression concurrent with the hibernation phenotype. By focusing on these differentially expressed genes in dwarf lemurs, we compare gene expression patterns in previously studied mammalian hibernators. Additionally, by employing evolutionary rate analysis, we find that hibernation-related genes do not evolve under positive selection in hibernating species relative to nonhibernators.This work was supported by grants from the Society of Integrative and Comparative Biology and Sigma Xi to S.L.F., a National Science Foundation Doctoral Research Improvement Grant (NSF-BCS 1455809 to A.D.Y. and S.L.F.), a grant from the Duke University Institute for Genome Science and Policy to A.D.Y., and funding from the Ministerio de Economía y Competitividad of the Spanish Government (BIO2009-08160 to J.L.V.C. and BFU2012-36820 to J.L.V.C. and M.M.A.); and Fundació ICREA to M.M.A.Peer reviewe