Project description:Identify shifts in gene expression relevant to torpor phenotypes and recovery following torpor in five tissues of the 13-lined ground squirrel. Sampled tissues and time points overlap with prior hibernation RNA-seq studies in 13-lined ground squirrel and other species, allowing for the analysis of conserved gene expression patterns in torpor.
Project description:Thirteen-lined ground squirrels (TLGS) are obligate hibernators that cycle between torpor (low metabolic rate and body temperature) and interbout euthermia (IBE; typical euthermic body temperature and metabolism) from late autumn to spring. Many physiological changes occur throughout hibernation, including a reduction in liver mitochondrial metabolism during torpor, which is reversed during arousal to interbout euthermia. Nuclear-encoded microRNA (small post-transcriptional regulator molecules) differ in abundance throughout TLGS hibernation and have been shown to regulate mitochondrial gene expression in mammalian cell culture (where they are referred to as mitomiRs). This study characterized differences in mitomiR profiles from TLGS liver mitochondria isolated during summer, torpor, and IBE, and predicted their mitochondrial targets. Using small RNA sequencing, differentially abundant mitomiRs were identified between hibernation states and, using qPCR analysis we quantified expression of predicted mitochondrial mRNA targets. Most differences in mitomiR abundances were seasonal (i.e. between summer and winter) with only one mitomiR differentially abundant between IBE and torpor. Multiple factor analysis revealed unique clustering of hibernation states, predominantly driven by mitomiR abundances, and nine of these differentially abundant mitomiRs had predicted mitochondrial RNA targets, including subunits of electron transfer system complexes I and IV, 12S rRNA and two tRNAs. Overall, mitomiRs were predicted to suppress expression of their mitochondrial targets and may have some involvement in regulating protein translation in mitochondria. This study found differences in mitomiR abundances between seasons and hibernation states of TLGS and suggests potential mechanisms in regulating the mitochondrial electron transfer system.
Project description:The identity of most functional elements in the mammalian genome and the phenotypes they impact are unclear. Here, we perform a genome-wide comparative analysis of patterns of accelerated evolution in species with highly distinctive traits to discover candidate functional elements for clinically important phenotypes. We identify accelerated regions (ARs) in the elephant, hibernating bat, orca, dolphin, naked mole rat and thirteen-lined ground squirrel lineages in mammalian conserved regions, uncovering ~33,000 elements that bind hundreds of different regulatory proteins in humans and mice. ARs in the elephant, the largest land mammal, are uniquely enriched at elephant DNA damage response genes and changed conserved regulatory sites. The genomic hotspot for elephant ARs is the E3 ligase subunit of the Fanconi Anemia Complex, a master regulator of DNA repair. Additionally, ARs in the six species are associated with specific human clinical phenotypes that have apparent concordance with overt traits in each species.