Genome assembly and gene expression in the American black bear provides new insights into the renal response to hibernation

Abstract

The prevalence of chronic kidney disease (CKD) is rising worldwide and 10-15% of the global population currently suffers from CKD and its complications. Given the increasing prevalence of CKD there is an urgent need to find novel treatment options. The American black bear (Ursus americanus) copes with months of lowered kidney function and metabolism during hibernation without the devastating effects on metabolism and other consequences observed in humans. In a biomimetic approach to better understand kidney adaptations and physiology in hibernating black bears, we established a high-quality genome assembly. Subsequent RNA-Seq analysis of kidneys comparing gene expression profiles in black bears entering (late fall) and emerging (early spring) from hibernation identified 169 protein-coding genes that were differentially expressed. Of these, 101 genes were downregulated and 68 genes were upregulated after hibernation. Fold changes ranged from 1.8-fold downregulation (RTN4RL2) to 2.4-fold upregulation (CISH). Most notable was the upregulation of cytokine suppression genes (SOCS2, CISH, and SERPINC1) and the lack of increased expression of cytokines and genes involved in inflammation. The identification of these differences in gene expression in the black bear kidney may provide new insights in the prevention and treatment of CKD.

Keywords: RNA-Seq; black bear; genome assembly; hibernation; kidney.

Figure 1

Sequencing depth and comparison of several characteristics of the black bear, panda, and polar bear genome assemblies. (A) Distribution of sequencing depth of the assembled genome (B) Completeness and contiguity of the assembly was estimated using CEGMA by screening against 248 universal eukaryotic single-copy genes. Results for the black bear (85.5% completeness) were comparable with the panda (88.7%) and polar bear (90.7%). (C) Density plot of the %GC content in the bear genomes comparing the black bear (solid line) with the panda (dashed line) and polar bear (dotted line). The narrower distribution in the black bear might indicate fewer repetitive sequences.

Figure 2

Comparison of different types of repeats between the black bear and several mammalian species shows a lower number of repeat sequences in the black bear.

Figure 3

Volcano plot of the differential gene expression between spring and fall with CISH, SLC01C1, and NDST3 being upregulated >2-fold in the spring compared with the fall.

Figure 4

Cluster analysis of the gene expression profiles showing the 50 genes with the lowest P-value.

Figure 5

The mouse kidney developmental expression profile at E12.5–E16.5 in their first two temporal principal components (PC1-2) with the mouse orthologues of genes that are downregulated after hibernation in blue and genes that are upregulated in red. Color figure is available at online version.