基因组测序解开裸鼢鼠未解之谜

BGI, the world's largest genomic organization, announced that an international team of researchers from Korea, China and the U.S. has, for the first time, demonstrated the physiology¹ and longevity² of the naked mole³ rats (NMR) in terms of genomics and transcriptomics（转录组学） . The results, published online in the journal Nature, provide an excellent opportunity to better understand the unique traits of naked mole rats and advance its use in biological and biomedical studies. With its wrinkled（有皱纹的） skin and double-saber buck⁴ 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 rodent⁵ known till now and are exceptionally resistant⁶ to cancer; they can live in full darkness, at low oxygen and high carbon dioxide concentrations; and they are unable to sustain thermogenesis（生热作用） 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. metabolic⁹ regulation, development, pain and behavior).

In this study, researchers utilized¹⁰ 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 gene⁷ set includes 22,561 genes⁸. 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. Utilizing¹¹ 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 transcripts¹² between different age groups and at exposure to different levels of oxygen concentration.

The researchers made further investigation¹³ 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 mechanism¹⁴. In addition, the unusual regulatory involvement of tumor¹⁵ suppressor p16Ink4a and p19Arf may be the key factor in NMR's cancer resistance, and mutation¹⁶ in the specificity of HIF1a and VHL may contribute to NMR's high tolerance¹⁷ 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 inactivated¹⁸ or missing in NMR, implicating¹⁹ that NMR's poor visual function may be caused by the deterioration²⁰（恶化，退化） of genes coding for various critical components²¹ of the visual system.

The genomic information of NMR provides a rich resource for researchers working in aging, cancer, eusociality（真社会制度） and many other areas. The data can be mined in numerous ways to uncover the molecular²² 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 mechanisms²³ of anti-aging, anti-cancer, adaptation to low oxygen environment and eusociality, with approaches of comparative genomics, comparative transcriptomics, and comparative methylation（甲基化） .

"The NMR genome will play an important role in functional²⁴ studies of NMR, which also will provide unprecedented²⁵ opportunities for exploring some of the most challenging questions in biology and medicine," stated Xiaodong Fang²⁶, 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."