Genome sequencing reveals insights into physiology and longevity of the naked mole rat

Journal name:
Nature
Volume:
479,
Pages:
223–227
Date published:
DOI:
doi:10.1038/nature10533
Received
Accepted
Published online

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.

At a glance

Figures

  1. Relationship of the NMR to other mammals.
    Figure 1: Relationship of the NMR to other mammals.

    a, Estimation of the time of divergence (with error range shown in parentheses) of the NMR and six other mammals based on orthology relationship. Distances are shown in millions of years. b, Expansion and contraction in gene families. Numbers designate the number of gene families that have expanded (green) and contracted (red) since the split from the common ancestor. The most recent common ancestor (MCRA) has 10,455 gene families.

  2. Common and unique NMR gene families.
    Figure 2: Common and unique NMR gene families.

    This Venn diagram shows unique and overlapping gene families in the NMR (H. glaber), rat (R. norvegicus), mouse (M. musculus) and human (H. sapiens).

  3. Unique changes in UCP1 sequences and their roles in thermoregulation.
    Figure 3: Unique changes in UCP1 sequences and their roles in thermoregulation.

    a, Alignment of mammalian UCP1 sequences. Amino acids unique to the NMR are highlighted in red, and conserved motifs in blue. b, Topology of UCP1. Regions affected in the NMR are highlighted. c, Structural model of UCP1. Location of the channel and the nucleotide-binding loop with altered sequences in the NMR are shown.

Accession codes

Primary accessions

Gene Expression Omnibus

Sequence Read Archive

References

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Author information

  1. These authors contributed equally to this work.

    • Eun Bae Kim,
    • Xiaodong Fang,
    • Alexey A. Fushan &
    • Zhiyong Huang

Affiliations

  1. Department of Bioinspired Science, Ewha Womans University, Seoul, 120-750, Korea

    • Eun Bae Kim,
    • Alexey A. Fushan &
    • Vadim N. Gladyshev
  2. BGI-Shenzhen, Shenzhen, 518083, China

    • Xiaodong Fang,
    • Zhiyong Huang,
    • Lijuan Han,
    • Xiaoqing Sun,
    • Pengcheng Yang,
    • Xiang Zhao,
    • Chunfang Peng,
    • Zhiqiang Xiong,
    • Yabing Zhu,
    • Yuanxin Chen,
    • Qiang Zhang,
    • Lan Yang,
    • Bo Wang,
    • Changlei Han,
    • Qiye Li,
    • Li Chen,
    • Wei Zhao,
    • Guojie Zhang &
    • Jun Wang
  3. Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA

    • Alexei V. Lobanov,
    • Stefano M. Marino,
    • Anton A. Turanov,
    • Sun Hee Yim,
    • Marina V. Kasaikina,
    • Nina Stoletzki,
    • Paz Polak,
    • Adam Kiezun,
    • Gregory V. Kryukov,
    • Shamil R. Sunyaev &
    • Vadim N. Gladyshev
  4. Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA

    • Gregory V. Kryukov,
    • Shamil R. Sunyaev &
    • Vadim N. Gladyshev
  5. Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA

    • Leonid Peshkin
  6. Rodent Histopathology Laboratory, Harvard Medical School, Boston, Massachusetts 02115, USA

    • Roderick T. Bronson
  7. Department of Physiology and The Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, Texas 78245, USA

    • Rochelle Buffenstein
  8. Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois 60607, USA

    • Thomas J. Park
  9. Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, DK-2200 Copenhagen N, Denmark

    • Jun Wang
  10. Department of Biology, University of Copenhagen, Copenhagen, DK-2200 Copenhagen N, Denmark

    • Jun Wang

Contributions

V.N.G. conceived the study. T.J.P. carried out animal work. A.A.T, M.V.K. and S.H.Y. prepared samples. X.F., Z.H., L.H., X.S., P.Y., X.Z., C.P., Z.X., Y.Z., Y.C., Q.Z., L.Y., B.W., C.H., Q.L., L.C., W.Z., G.Z. and J.W. performed genome sequencing and assembly. X.F., G.Z., and J.W. supervised genome sequencing and assembly. E.B.K., X.F., A.A.F., Z.H., A.V.L., S.M.M., L.P., G.Z. and V.N.G. performed genome and transcriptome analyses. Z.H., N.S., P.P., A.K. and S.R.S. carried out genetic analyses. G.V.K., R.T.B. and R.B. discussed the data. All authors contributed to data interpretation. V.N.G. wrote the paper with significant contributions from E.B.K., X.F., A.A.F., Z.H., S.R.S. and G.Z., and input from all authors.

Competing financial interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to:

The NMR whole-genome shotgun project has been deposited at DDBJ/EMBL/GenBank under the accession number AFSB00000000. The version described in this paper is the first version, AFSB01000000. The mitochondrial sequence has been deposited at GenBank under the accession number JN242813. All short-read data have been deposited into the Short Read Archive (http://www.ncbi.nlm.nih.gov/sra) under the accession number SRA030468. Raw sequencing data of the transcriptome have been deposited in the Gene Expression Omnibus with the accession number GSE30337.

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Supplementary information

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  1. Supplementary Information (6.9M)

    The file contains Supplementary Text, Supplementary Figures 1-30 with legends, Supplementary Tables 1-11, 14-15, 18-20, 24 (see separate zip file for tables 12, 14, 16, 17, 21, 22, 23 and 25-31) and additional references (see page 1 for content).

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    The zip file contains Supplementary Tables 12, 13, 16, 17, 21, 22, 23 and 25-31.

Comments

  1. Report this comment #27744

    Michael Lerman said:

    This is a fantastic achievement! The work was well planned and perfectly executed!. This treasure trove will be used to understand the unique biological features of these remarkable animals and more importantly to gain unique insights into aging and cancer.
    Michael Lerman, Ph.D., M.D.

  2. Report this comment #28344

    Dov Henis said:

    Aging Is Also An E/m Matter,
    Like each and all things in the universe.

    A.
    There is neither alchemy nor mystery in aging. Aging, like everything else in the universe, is an E/m, energy/mass, matter.

    The universe is a two-poles affair. It evolves cyclically between two poles: an all-mass Big-Bang pole and a nearly-all-energy pole. Presently all the singularity mass is reconverting to energy, to energy that drives apart the galaxies clusters. In the energy-mass dualism mass thus diminishes as energy increases and the speed of separating clusters is, in accordance with Newton, accelerating.

    Since thus every mass format, the totality of its components, are destined to reconvert to energy, the format must continuously take in energy or mass to postpone its own constitutional reconversion events. The in-takers of energy range from the biggest black hole to the smallest particle, including living organisms. This is what ?natural selection? is all about. Natural selection is about ALL the E/m reconversions in the universe.

    B.
    See ? Aging Seen Without The Emperor?s New Clothes?
    March 9, 2009
    http://ouroboros.wordpress.com/2009/02/18/the-link-between-protein-synthesis-and-mitochondrial-degradation-and-towards-a-unified-mechanism-of-aging/#comment-4750

    C.
    Slowing aging is postponing of mass reconversion(s) event(s) of organisms, including genes/genomes, and/or of the other system?s components.

    About time that ?scientists? refresh conceptions and comprehensions and attitudes and research plans and anti-subversion peer-reviewing. Let their science evolve?

    Dov Henis
    (comments from 22nd century)
    http://universe-life.com/

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