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Evolution and lineage dynamics of a transmissible cancer in Tasmanian devils
PLOS Biology ( IF 7.8 ) Pub Date : 2020-11-24 , DOI: 10.1371/journal.pbio.3000926
Young Mi Kwon 1 , Kevin Gori 1 , Naomi Park 2 , Nicole Potts 1 , Kate Swift 3 , Jinhong Wang 1 , Maximilian R Stammnitz 1 , Naomi Cannell 1 , Adrian Baez-Ortega 1 , Sebastien Comte 4, 5 , Samantha Fox 6, 7 , Colette Harmsen 3 , Stewart Huxtable 6 , Menna Jones 4 , Alexandre Kreiss 8 , Clare Lawrence 6 , Billie Lazenby 6 , Sarah Peck 6 , Ruth Pye 8 , Gregory Woods 8 , Mona Zimmermann 1 , David C Wedge 9 , David Pemberton 6 , Michael R Stratton 2 , Rodrigo Hamede 4, 10 , Elizabeth P Murchison 1
Affiliation  

Devil facial tumour 1 (DFT1) is a transmissible cancer clone endangering the Tasmanian devil. The expansion of DFT1 across Tasmania has been documented, but little is known of its evolutionary history. We analysed genomes of 648 DFT1 tumours collected throughout the disease range between 2003 and 2018. DFT1 diverged early into five clades, three spreading widely and two failing to persist. One clade has replaced others at several sites, and rates of DFT1 coinfection are high. DFT1 gradually accumulates copy number variants (CNVs), and its telomere lengths are short but constant. Recurrent CNVs reveal genes under positive selection, sites of genome instability, and repeated loss of a small derived chromosome. Cultured DFT1 cell lines have increased CNV frequency and undergo highly reproducible convergent evolution. Overall, DFT1 is a remarkably stable lineage whose genome illustrates how cancer cells adapt to diverse environments and persist in a parasitic niche.



中文翻译:


塔斯马尼亚袋獾传染性癌症的进化和谱系动态



袋獾面部肿瘤 1 (DFT1) 是一种传染性癌症克隆,危及塔斯马尼亚袋獾。 DFT1 在塔斯马尼亚的扩张已有记录,但对其进化历史却知之甚少。我们分析了 2003 年至 2018 年间在整个疾病范围内收集的 648 个 DFT1 肿瘤的基因组。DFT1 早期分化为五个分支,其中三个广泛传播,两个未能持续存在。一个进化枝已在多个地点取代了其他进化枝,并且 DFT1 共感染率很高。 DFT1逐渐积累拷贝数变异(CNV),其端粒长度虽短但恒定。反复出现的 CNV 揭示了正向选择下的基因、基因组不稳定位点以及小衍生染色体的反复丢失。培养的 DFT1 细胞系具有增加的 CNV 频率并经历高度可重复的趋同进化。总体而言,DFT1 是一个非常稳定的谱系,其基因组说明了癌细胞如何适应不同的环境并在寄生生态位中持续存在。

更新日期:2020-11-25
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