Transcriptome Sequencing of the Blind Subterranean Mole Rat, Spalax galili: Utility and Potential for the Discovery of Novel Evolutionary Patterns

Malik, Assaf; Korol, Abraham B.; Hübner, Sariel; Hernandez, Alvaro G.; Thimmapuram, Jyothi; Ali, Shahjahan; Glaser, Fabian; Paz, Arnon; Avivi, Aaron; Band, Mark

doi:10.1371/journal.pone.0021227

Cited by 33 publications

(28 citation statements)

References 62 publications

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“…Noteworthy, as part of a S. galili transcriptome sequencing project carried out recently (Malik et al, 2011), different types of novel S. galili transcribed regions were found in stress-related genes, with no evidence for conservation beyond the S. ehrenbergi species complex. One intriguing example of a novel exon was found in the gene Tripeptidyl-Peptidase II (TPPII), which was suggested to be involved in the response to ROS and DNA damage (Preta et al, 2009).…”

Section: Nrf2 As a Master Regulator Of Antioxidant Defensementioning

confidence: 99%

Living with stress: Regulation of antioxidant defense genes in the subterranean, hypoxia-tolerant mole rat, Spalax

Schülke

Dreidax

Malik

et al. 2012

Gene

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Section: Nrf2 As a Master Regulator Of Antioxidant Defensementioning

confidence: 99%

Living with stress: Regulation of antioxidant defense genes in the subterranean, hypoxia-tolerant mole rat, Spalax

Schülke

Dreidax

Malik

et al. 2012

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“…Noteworthy are VEGF , constitutively highly expressed as compared to rats [7]; p53 that harbors substitutions in the DNA-binding site, identical to the most common p53 mutations in tumors; however, in Spalax it renders a bias against apoptosis but favors cell cycle arrest/DNA repair both in vitro and in vivo [8]; and a unique Spalax heparanase splice variant that was shown to decrease tumor size in mice by a factor of 7 and reduce metastatic activity compared to native mice heparanase [9]. Furthermore, assessment of Spalax transcriptome assembly and expression data has revealed enrichment of genes that overlap cancer resistance, apoptosis, angiogenesis pathways and hypoxia-tolerance [10,11]. This suggests that Spalax is potentially resistant to malignant transformation.…”

Section: Introductionmentioning

confidence: 99%

Pronounced cancer resistance in a subterranean rodent, the blind mole-rat, Spalax: in vivo and in vitroevidence

Manov

Hirsh

Iancu³

et al. 2013

BMC Biol

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106

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BackgroundSubterranean blind mole rats (Spalax) are hypoxia tolerant (down to 3% O2), long lived (>20 years) rodents showing no clear signs of aging or aging related disorders. In 50 years of Spalax research, spontaneous tumors have never been recorded among thousands of individuals. Here we addressed the questions of (1) whether Spalax is resistant to chemically-induced tumorigenesis, and (2) whether normal fibroblasts isolated from Spalax possess tumor-suppressive activity.ResultsTreating animals with 3-Methylcholantrene (3MCA) and 7,12-Dimethylbenz(a) anthracene/12-O-tetradecanoylphorbol-13-acetate (DMBA/TPA), two potent carcinogens, confirmed Spalax high resistance to chemically induced cancers. While all mice and rats developed the expected tumors following treatment with both carcinogens, among Spalax no tumors were observed after DMBA/TPA treatment, while 3MCA induced benign fibroblastic proliferation in 2 Spalax individuals out of12, and only a single animal from the advanced age group developed malignancy 18 months post-treatment. The remaining animals are still healthy 30 months post-treatment. In vitro experiments showed an extraordinary ability of normal Spalax cultured fibroblasts to restrict malignant behavior in a broad spectrum of human-derived and in newly isolated Spalax 3MCA-induced cancer cell lines. Growth of cancer cells was inhibited by either direct interaction with Spalax fibroblasts or with soluble factors released into culture media and soft agar. This was accompanied by decreased cancer cell viability, reduced colony formation in soft agar, disturbed cell cycle progression, chromatin condensation and mitochondrial fragmentation. Cells from another cancer resistant subterranean mammal, the naked mole rat, were also tested for direct effect on cancer cells and, similar to Spalax, demonstrated anti-cancer activity. No effect on cancer cells was observed using fibroblasts from mouse, rat or Acomys. Spalax fibroblast conditioned media had no effect on proliferation of noncancerous cells.ConclusionsThis report provides pioneering evidence that Spalax is not only resistant to spontaneous cancer but also to experimentally induced cancer, and shows the unique ability of Spalax normal fibroblasts to inhibit growth and kill cancer cells, but not normal cells, either through direct fibroblast-cancer cell interaction or via soluble factors. Obviously, along with adaptation to hypoxia, Spalax has evolved efficient anti-cancer mechanisms yet to be elucidated. Exploring the molecular mechanisms allowing Spalax to survive in extreme environments and to escape cancer as well as to kill homologous and heterologous cancer cells may hold the key for understanding the molecular nature of host resistance to cancer and identify new anti-cancer strategies for treating humans.

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“…We compiled newly obtained transcriptome data from the zokor and the bamboo rat alongside the published transcriptome assembly from the Middle East mole rat [15], and provided a conclusive resolution of interrelationships of the three subfamilies within the family Spalacidae using a phylogenomic approach.…”

Section: Introductionmentioning

confidence: 99%

Transcriptome sequencing and phylogenomic resolution within Spalacidae (Rodentia)

et al. 2014

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BackgroundSubterranean mammals have been of great interest for evolutionary biologists because of their highly specialized traits for the life underground. Owing to the convergence of morphological traits and the incongruence of molecular evidence, the phylogenetic relationships among three subfamilies Myospalacinae (zokors), Spalacinae (blind mole rats) and Rhizomyinae (bamboo rats) within the family Spalacidae remain unresolved. Here, we performed de novo transcriptome sequencing of four RNA-seq libraries prepared from brain and liver tissues of a plateau zokor (Eospalax baileyi) and a hoary bamboo rat (Rhizomys pruinosus), and analyzed the transcriptome sequences alongside a published transcriptome of the Middle East blind mole rat (Spalax galili). We characterize the transcriptome assemblies of the two spalacids, and recover the phylogeny of the three subfamilies using a phylogenomic approach.ResultsApproximately 50.3 million clean reads from the zokor and 140.8 million clean reads from the bamboo ratwere generated by Illumina paired-end RNA-seq technology. All clean reads were assembled into 138,872 (the zokor) and 157,167 (the bamboo rat) unigenes, which were annotated by the public databases: the Swiss-prot, Trembl, NCBI non-redundant protein (NR), NCBI nucleotide sequence (NT), Gene Ontology (GO), Cluster of Orthologous Groups (COG), and Kyoto Encyclopedia of Genes and Genomes (KEGG). A total of 5,116 nuclear orthologous genes were identified in the three spalacids and mouse, which was used as an outgroup. Phylogenetic analysis revealed a sister group relationship between the zokor and the bamboo rat, which is supported by the majority of gene trees inferred from individual orthologous genes, suggesting subfamily Myospalacinae is more closely related to subfamily Rhizomyinae. The same topology was recovered from concatenated sequences of 5,116 nuclear genes, fourfold degenerate sites of the 5,116 nuclear genes and concatenated sequences of 13 protein coding mitochondrial genes.ConclusionsThis is the first report of transcriptome sequencing in zokors and bamboo rats, representing a valuable resource for future studies of comparative genomics in subterranean mammals. Phylogenomic analysis provides a conclusive resolution of interrelationships of the three subfamilies within the family Spalacidae, and highlights the power of phylogenomic approach to dissect the evolutionary history of rapid radiations in the tree of life.

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Transcriptome Sequencing of the Blind Subterranean Mole Rat, Spalax galili: Utility and Potential for the Discovery of Novel Evolutionary Patterns

Cited by 33 publications

References 62 publications

Living with stress: Regulation of antioxidant defense genes in the subterranean, hypoxia-tolerant mole rat, Spalax

Living with stress: Regulation of antioxidant defense genes in the subterranean, hypoxia-tolerant mole rat, Spalax

Pronounced cancer resistance in a subterranean rodent, the blind mole-rat, Spalax: in vivo and in vitroevidence

Transcriptome sequencing and phylogenomic resolution within Spalacidae (Rodentia)

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