title: Genome maintenance and bioenergetics of the long-lived hypoxia-tolerant and cancer-resistant blind mole rat, Spalax: a cross-species analysis of brain transcriptome.
abstract: The subterranean blind mole rat, Spalax, experiences acute hypoxia-reoxygenation cycles in its natural subterranean habitat. At the cellular level, these conditions are known to promote genomic instability, which underlies both cancer and aging. However, Spalax is a long-lived animal and is resistant to both spontaneous and induced cancers. To study this apparent paradox we utilized a computational procedure that allows detecting differences in transcript abundance between Spalax and the closely related above-ground Rattus norvegicus in individuals of different ages. Functional enrichment analysis showed that Spalax whole brain tissues maintain significantly higher normoxic mRNA levels of genes associated with DNA damage repair and DNA metabolism, yet keep significantly lower mRNA levels of genes involved in bioenergetics. Many of the genes that showed higher transcript abundance in Spalax are involved in DNA repair and metabolic pathways that, in other species, were shown to be downregulated under hypoxia, yet are required for overcoming replication- and oxidative-stress during the subsequent reoxygenation. We suggest that these differentially expressed genes may prevent the accumulation of DNA damage in mitotic and post-mitotic cells and defective resumption of replication in mitotic cells, thus maintaining genome integrity as an adaptation to acute hypoxia-reoxygenation cycles.
authors.affiliation: Institue of Evolution, University of Haifa, Haifa 3498838, Israel.|Bioinformatics Core Unit, University of Haifa, Haifa 3498838, Israel.
authors.forename: Assaf
authors.initials: A
authors.lastname: Malik
authors.affiliation: Institue of Evolution, University of Haifa, Haifa 3498838, Israel.|Deparment of Evolutionary and Environmental Biology, University of Haifa, Haifa 3498838, Israel.
authors.forename: Vered
authors.initials: V
authors.lastname: Domankevich
authors.affiliation: BGI-Tech, BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Han
authors.initials: H
authors.lastname: Lijuan
authors.affiliation: BGI-Tech, BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Xiaodong
authors.affiliation: Institue of Evolution, University of Haifa, Haifa 3498838, Israel.|Deparment of Evolutionary and Environmental Biology, University of Haifa, Haifa 3498838, Israel.
authors.forename: Abraham
authors.initials: A
authors.lastname: Korol
authors.affiliation: Institue of Evolution, University of Haifa, Haifa 3498838, Israel.
authors.forename: Aaron
authors.initials: A
authors.lastname: Avivi
authors.affiliation: Institue of Evolution, University of Haifa, Haifa 3498838, Israel.|Deparment of Evolutionary and Environmental Biology, University of Haifa, Haifa 3498838, Israel.
authors.forename: Imad
authors.initials: I
authors.lastname: Shams
mesh_terms: D000220:Adaptation, Biological; D000818:Animals; D001921:Brain / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods; D060467:Disease Resistance; D004734:Energy Metabolism; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D000860:Hypoxia / Q000235:genetics* / Q000378:metabolism*; D015203:Reproducibility of Results; D017423:Sequence Analysis, RNA; D015398:Signal Transduction; D046308:Spalax / Q000235:genetics* / Q000378:metabolism*; D013045:Species Specificity; D059467:Transcriptome