Genome sequencing unlocks the mysteries of naked mole rat

With its wrinkled skin and double-saber buck teeth, the naked mole rat may not be among the most beautiful animals, but they are exceptional in other ways. They are the longest-lived rodent known till now and are exceptionally resistant to cancer; they can live in full darkness, at low oxygen and high carbon dioxide concentrations; and they are unable to sustain thermogenesis or feel certain types of pain. These unique features make naked mole rats particularly attractive to scientists as emerging models for research on aging and cancer, as well as other biological activities or conditions (e.g. metabolic regulation, development, pain and behavior).

In this study, researchers utilized the whole-genome shotgun (WGS) sequencing strategy and next-generation sequencing system to sequence the genome of an individual male naked mole rat. The NMR genome is approximately 2.6 Gb, and the predicted NMR gene set includes 22,561 genes. By sequencing the genome, the researchers demonstrated that the ancestor of NMR split from the ancestors of mice and rats about 73 million years ago, and 93% of the NMR genome shows synteny to human, mouse or rat genomes. Utilizing comparative transcriptome analysis, some genes related to anti-aging and adaptation to a low oxygen environment were identified based on the different expression levels of NMR transcripts between different age groups and at exposure to different levels of oxygen concentration.

The researchers made further investigation and found several important genes related to the exceptional traits of NMR. The stable gene expression of TERT and other genes, regardless of age, may be related to NMR's longevity mechanism. In addition, the unusual regulatory involvement of tumor suppressor p16Ink4a and p19Arf may be the key factor in NMR's cancer resistance, and mutation in the specificity of HIF1a and VHL may contribute to NMR's high tolerance to a low oxygen environment. At least 10% of the approximately 200 genes associated with visual perception in humans and mice were found to be inactivated or missing in NMR, implicating that NMR's poor visual function may be caused by the deterioration of genes coding for various critical components of the visual system.

The genomic information of NMR provides a rich resource for researchers working in aging, cancer, eusociality and many other areas. The data can be mined in numerous ways to uncover the molecular basis for the extraordinary traits of this most unusual mammal. To achieve a more comprehensive insight into NMR's exceptional traits, the international team will continue to explore the molecular mechanisms of anti-aging, anti-cancer, adaptation to low oxygen environment and eusociality, with approaches of comparative genomics, comparative transcriptomics, and comparative methylation.

"The NMR genome will play an important role in functional studies of NMR, which also will provide unprecedented opportunities for exploring some of the most challenging questions in biology and medicine," stated Xiaodong Fang, Leader of non-model organisms group at BGI and the co-leading author of the study. "We believe that NMR will become a new model in biological and biomedical research in the near future."