Transcriptomics in the wild: Hibernation physiology in free‐ranging dwarf lemurs

Abstract

Hibernation is an adaptive strategy some mammals use to survive highly seasonal or unpredictable environments. We present the first investigation on the transcriptomics of hibernation in a natural population of primate hibernators: Crossley's dwarf lemurs (Cheirogaleus crossleyi). Using capture-mark-recapture techniques to track the same animals over a period of 7 months in Madagascar, we used RNA-seq to compare gene expression profiles in white adipose tissue (WAT) during three distinct physiological states. We focus on pathway analysis to assess the biological significance of transcriptional changes in dwarf lemur WAT and, by comparing and contrasting what is known in other model hibernating species, contribute to a broader understanding of genomic contributions of hibernation across Mammalia. The hibernation signature is characterized by a suppression of lipid biosynthesis, pyruvate metabolism and mitochondrial-associated functions, and an accumulation of transcripts encoding ribosomal components and iron-storage proteins. The data support a key role of pyruvate dehydrogenase kinase isoenzyme 4 (PDK4) in regulating the shift in fuel economy during periods of severe food deprivation. This pattern of PDK4 holds true across representative hibernating species from disparate mammalian groups, suggesting that the genetic underpinnings of hibernation may be ancestral to mammals.

Tropical heterothermy is “cool”: The expression of daily torpor and hibernation in primates

“…), [108][109][110][111][112] American black bears (Ursus americanus), 113,114 little brown bats (Myotis lucifugus) 115 and recently in two different species of dwarf lemurs (Cheirogaleus medius and Cheirogaleus crossleyi). 21,116 These studies reveal specific genes that might play a key role in the hibernation phenotype and similar pathways are upregulated in predictable ways in all hibernating species studied to date. Of import are genes involved in lipid and carbohydrate metabolism, blood coagulation, and circadian rhythms.…”

“…19,20 Differences in the physiological tuning of hibernation and metabolic regulation may, in fact, signal variation in underlying mechanisms brought about by unique evolutionary histories, though it is increasingly thought that the capacity for heterothermy is ancestral in mammals, having been suppressed in lineages and species that are apparently nonheterothermic. 21…”

Oxygen and brain death; back from the brink

“…Originally thought to be restricted to cold-adapted mammals, hibernation has also been observed in primates (dwarf lemurs; Blanco, Dausmann, Ranaivoarisoa, & Yoder, 2013;Dausmann, Glos, Ganzhorn, & Heldmaier, 2004), implying that perhaps we humans have the ability to hibernate, which has beneficial applications in medicine and longterm space exploration (Chouker, Bereiter-Hahn, Singer, & Heldmaier, 2019). Central metabolic roles for pyruvate dehydrogenase kinase isoenzyme 4 (Faherty, Villanueva-Canas, Blanco, Alba, & Yoder, 2018) and hibernation-specific protein (HP20 complex; Kondo et al, 2006) have been suggested as ancestral 'hibernation signatures' that contribute to mammalian brain signalling and neuroprotection.…”

Conservation genomic analysis reveals ancient introgression and declining levels of genetic diversity in Madagascar’s hibernating dwarf lemurs

“…sib). NPY2R is a gene that was identified to be upregulated in the fat vs torpor phases of Faherty et al (2018); NPY2R was identified in an introgressed region between C. med/C. sib.…”