Abstract
The blind subterranean mole rat Spalax shows a remarkable tolerance to hypoxia, cancer-resistance and longevity. Unravelling the genomic basis of these adaptations will be important for biomedical applications. RNA-Seq gene expression data were obtained from normoxic and hypoxic Spalax and rat liver tissue. Hypoxic Spalax broadly downregulates genes from major liver function pathways. This energy-saving response is likely a crucial adaptation to low oxygen levels. In contrast, the hypoxia-sensitive rat shows massive upregulation of energy metabolism genes. Candidate genes with plausible connections to the mole rat’s phenotype, such as important key genes related to hypoxia-tolerance, DNA damage repair, tumourigenesis and ageing, are substantially higher expressed in Spalax than in rat. Comparative liver transcriptomics highlights the importance of molecular adaptations at the gene regulatory level in Spalax and pinpoints a variety of starting points for subsequent functional studies.
Highlights
Much of our knowledge on biological processes and principles, especially in biomedical research, is based on studies in a rather small number of model organisms such as mouse and rat
The main results of our comparative RNA-Seq analysis should be largely independent of technical biases, since they were validated using different ortholog gene annotation pipelines, read-mapping algorithms and tools to identify and functionally interpret differential gene expression
Analysing differential gene expression in liver after hypoxic exposure of animals, we found more than twice as many genes being upregulated under hypoxia in rat (26.9%) than in Spalax (12%)
Summary
Much of our knowledge on biological processes and principles, especially in biomedical research, is based on studies in a rather small number of model organisms such as mouse and rat. Two rodents that have attracted attention as emerging models for biomedical research are the blind mole rat Spalax and the naked mole rat Heterocephalus glaber[3]; each of which shares a set of unique biological traits highly relevant for human health Both taxa are tolerant to extreme environmental conditions such as strong hypoxia and reoxygenation. In addition we aimed to identify genes which are differentially expressed constitutively between Spalax and rat liver tissue under normoxic, non-stress conditions
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