Unraveling the message: insights into comparative genomics of the naked mole-rat.
Unraveling the message: insights into comparative genomics of the naked mole-rat.
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DOI：
10.1007/s00335-016-9648-5
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发表时间：
2016-08
期刊：
影响因子：
--
通讯作者：
Buffenstein R
中科院分区：
文献类型：
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作者：
Lewis KN;Soifer I;Melamud E;Roy M;McIsaac RS;Hibbs M;Buffenstein R
动物已经进化到在不同的环境中生存，甚至茁壮成长。遗传适应可能间接地创造了表型，这也导致了更长的寿命。这种现象的一个例子是超乎寻常的长寿裸鼹鼠。这种严格的地下啮齿类动物耐受低氧、高碳酸血症和土壤毒素。裸鼠对癌症也表现出明显的抵抗力，许多生理特征的衰退程度也有所减弱，这些特征往往随着哺乳动物的年龄增长而衰退。阐明导致其独特表型的机制将有助于更好地理解地下生态生理学和衰老生物学。在这方面，比较基因组学可能是一个有用的工具。自从2011年裸露的鼹鼠基因组组发表以来，对基因组和转录组数据的分析使人们能够更清楚地了解鼹鼠的进化史，并提出了可能解释该物种非凡长寿和独特健康特征的分子途径(例如，NRF2信号激活和DNA损伤修复机制)。然而，仔细的审查和重新分析表明，一些已确定的特征是由于裸鼠基因组的不正确或不精确的注释和组装造成的：此外，当分析包括其他更密切相关的物种时，其中一些结论(例如，参与抗癌和无毛的基因)被拒绝。我们描述了更好的研究设计、改进的基因组测序技术以及新的生物信息学和数据分析工具的结合如何改进比较基因组学，并最终弥合传统模式生物和非模式生物之间的差距。
Animals have evolved to survive, and even thrive, in different environments. Genetic adaptations may have indirectly created phenotypes that also resulted in a longer lifespan. One example of this phenomenon is the preternaturally long-lived naked mole-rat. This strictly subterranean rodent tolerates hypoxia, hypercapnia, and soil-based toxins. Naked mole-rats also exhibit pronounced resistance to cancer and an attenuated decline of many physiological characteristics that often decline as mammals age. Elucidating mechanisms that give rise to their unique phenotypes will lead to better understanding of subterranean ecophysiology and biology of aging. Comparative genomics could be a useful tool in this regard. Since the publication of a naked mole-rat genome assembly in 2011, analyses of genomic and transcriptomic data have enabled a clearer understanding of mole-rat evolutionary history and suggested molecular pathways (e.g., NRF2-signaling activation and DNA damage repair mechanisms) that may explain the extraordinarily longevity and unique health traits of this species. However, careful scrutiny and re-analysis suggest that some identified features result from incorrect or imprecise annotation and assembly of the naked mole-rat genome: in addition, some of these conclusions (e.g., genes involved in cancer resistance and hairlessness) are rejected when the analysis includes additional, more closely related species. We describe how the combination of better study design, improved genomic sequencing techniques, and new bioinformatic and data analytical tools will improve comparative genomics and ultimately bridge the gap between traditional model and nonmodel organisms.