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Genome sequencing reveals insights into physiology and longevity of the naked mole rat
Open accessAbstract
The mouse-sized naked mole rat (Heterocephalus glaber) is a very unusual mammal. It is a social animal, living in groups in burrows beneath arid African deserts. It can live for 30 or more years in atmospheres with low oxygen and high carbon dioxide, and is remarkably resistant to cancer. So the genome sequence, published in this issue, might be expected to contain some intriguing characteristics. Analysis of the genome and its transcriptome reveals unusual genomic features and molecular adaptations including strategies for improved genome stability, low mutation rate and improved protein maintenance. The data also reveal molecular adaptations consistent with poor visual function, poikilothermy, hairlessness, circadian rhythms, taste sensing and insensitivity to low oxygen. The naked mole rat (Heterocephalus glaber) is a strictly subterranean, extraordinarily long-lived eusocial mammal1. Although it is the size of a mouse, its maximum lifespan exceeds 30 years, making this animal the longest-living rodent. Naked mole rats show negligible senescence, no age-related increase in mortality, and high fecundity until death2. In addition to delayed ageing, they are resistant to both spontaneous cancer and experimentally induced tumorigenesis3,4. Naked mole rats pose a challenge to the theories that link ageing, cancer and redox homeostasis. Although characterized by significant oxidative stress5, the naked mole rat proteome does not show age-related susceptibility to oxidative damage or increased ubiquitination6. Naked mole rats naturally reside in large colonies with a single breeding female, the ‘queen’, who suppresses the sexual maturity of her subordinates7. They also live in full darkness, at low oxygen and high carbon dioxide concentrations8, and are unable to sustain thermogenesis9 nor feel certain types of pain10,11. Here we report the sequencing and analysis of the naked mole rat genome, which reveals unique genome features and molecular adaptations consistent with cancer resistance, poikilothermy, hairlessness and insensitivity to low oxygen, and altered visual function, circadian rythms and taste sensing. This information provides insights into the naked mole rat’s exceptional longevity and ability to live in hostile conditions, in the dark and at low oxygen. The extreme traits of the naked mole rat, together with the reported genome and transcriptome information, offer opportunities for understanding ageing and advancing other areas of biological and biomedical research.
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“Interestingly, the genome of the longest-lived rodent, the naked mole rat, contains fewer retrotransposons than other rodent genomes108; whereas the genomes of long-lived bats are replete with transposable elements109.”
From The role of retrotransposable elements in ageing and age-associated diseases (2021) · cites this paper as [108]
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Metadata
- Authors
- Kim, E. B., Fang, X., Fushan, A. A., Huang, Z., Lobanov, A. V., Han, L., Marino, S. M., Sun, X., Turanov, A. A., Yang, P., Yim, S. H., Zhao, X., Kasaikina, M. V., Stoletzki, N., Peng, C., Polak, P., Xiong, Z., Kiezun, A., Zhu, Y., Chen, Y., Kryukov, G. V., Zhang, Q., Peshkin, L., Yang, L., Bronson, R. T., Buffenstein, R., Wang, B., Han, C., Li, Q., Chen, L., Zhao, W., Sunyaev, S. R., Park, T. J., Zhang, G., Wang, J., & Gladyshev, V. N.
- Affiliations
- Ewha Womans University (KR)
- BGI Group (China) (CN)
- Brigham and Women's Hospital (US)
- Broad Institute (US)
- Harvard University (US)
- The University of Texas at San Antonio Health Science Center (US)
- University of Illinois Chicago (US)
- Corresponding author
- Zhang, Guojie
- Wang, Jun
- Gladyshev, Vadim N.
- ORCID
- Kim, Eun Bae
- Fang, Xiaodong
- Huang, Zhiyong
- Lobanov, Alexei V.
- Han, Lijuan
- Marino, Stefano M.
- Sun, Xiaoqing
- Yang, Pengcheng
- Yim, Sun Hee
- Zhao, Xiang
- Stoletzki, Nina
- Polak, Paz
- Xiong, Zhiqiang
- Zhu, Yabing
- Chen, Yuanxin
- Kryukov, Gregory V.
- Peshkin, Leonid
- Bronson, Roderick T.
- Buffenstein, Rochelle
- Wang, Bo
- Li, Qiye
- Chen, Li
- Zhao, Wei
- Sunyaev, Shamil R.
- Park, Thomas J.
- Zhang, Guojie
- Wang, Jun
- Gladyshev, Vadim N.
- Venue
- Nature
- Published
- 2011-10-12
- Volume
- 479
- Issue
- 7372
- Pages
- 223-227
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3319411
- OpenAlex
- W2026944808
- Semantic Scholar
- f13611166eb11cefa0156fe963647ed6e0952741
- Cited by
- 576
- References
- 30
- Citations by year
- 2026: 17 · 2025: 18 · 2024: 23 · 2023: 34 · 2022: 41 · 2021: 50 · 2020: 71 · 2019: 31 · 2018: 41 · 2017: 34 · 2016: 41 · 2015: 56 · 2014: 43 · 2013: 44 · 2012: 30
- FWCI
- 13.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Science Foundation (0744979)
- National Natural Science Foundation of China (30725008)
- National Institutes of Health
- National Institute on Aging (R01AG038004, R01AG021518)
- National Cancer Institute (R01CA080946)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
- Keywords
- naked mole-rat, genome sequence, tumor resistance, longevity, aging, low oxygen tolerance, poikilothermy, hairlessness, visual function, circadian rhythm, taste sensing, eusociality, genome stability, oxidative stress, ubiquitination, subterranean mammals
- MeSH terms
- Uncoupling Protein 1, Adaptation, Physiological, Aging, Amino Acid Sequence, Animals, Body Temperature Regulation, Carbon Dioxide, Circadian Rhythm, Darkness, Genes, Humans, Ion Channels, Longevity, Male, Molecular Sequence Data, Oxygen, Taste, Visual Perception, Mutagenesis, Genome, Mole Rats, Genomics, Mitochondrial Proteins, Genomic Instability, Transcriptome
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