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比较细胞遗传学作图和端粒分析为恶魔面部肿瘤 2 提供进化预测。

Comparative Cytogenetic Mapping and Telomere Analysis Provide Evolutionary Predictions for Devil Facial Tumour 2.

机构信息

Institute for Applied Ecology, University of Canberra, Canberra, ACT 2617, Australia.

出版信息

Genes (Basel). 2020 Apr 28;11(5):480. doi: 10.3390/genes11050480.

Abstract

The emergence of a second transmissible tumour in the Tasmanian devil population, devil facial tumour 2 (DFT2), has prompted questions on the origin and evolution of these transmissible tumours. We used a combination of cytogenetic mapping and telomere length measurements to predict the evolutionary trajectory of chromosome rearrangements in DFT2. Gene mapping by fluorescence in situ hybridization (FISH) provided insight into the chromosome rearrangements in DFT2 and identified the evolution of two distinct DFT2 lineages. A comparison of devil facial tumour 1 (DFT1) and DFT2 chromosome rearrangements indicated that both started with the fusion of a chromosome, with potentially critically short telomeres, to chromosome 1 to form dicentric chromosomes. In DFT1, the dicentric chromosome resulted in breakage-fusion-bridge cycles leading to highly rearranged chromosomes. In contrast, the silencing of a centromere on the dicentric chromosome in DFT2 stabilized the chromosome, resulting in a less rearranged karyotype than DFT1. DFT2 retains a bimodal distribution of telomere length dimorphism observed on Tasmanian devil chromosomes, a feature lost in DFT1. Using long term cell culture, we observed homogenization of telomere length over time. We predict a similar homogenization of telomere lengths occurred in DFT1, and that DFT2 is unlikely to undergo further substantial rearrangements due to maintained telomere length.

摘要

塔斯马尼亚恶魔种群中第二种可传播肿瘤——恶魔面部肿瘤 2(DFT2)的出现,引发了人们对这些可传播肿瘤的起源和进化的疑问。我们使用细胞遗传学作图和端粒长度测量的组合来预测 DFT2 染色体重排的进化轨迹。荧光原位杂交(FISH)的基因作图提供了对 DFT2 染色体重排的深入了解,并确定了两种不同的 DFT2 谱系的进化。DFT1 和 DFT2 染色体重排的比较表明,两者都始于一条染色体与 1 号染色体融合,形成双着丝粒染色体,这些染色体可能具有极短的端粒。在 DFT1 中,双着丝粒染色体导致断裂-融合-桥循环,导致高度重排的染色体。相比之下,DFT2 中双着丝粒染色体上一个着丝粒的沉默稳定了染色体,导致其核型比 DFT1 重排程度更低。DFT2 保留了塔斯马尼亚恶魔染色体上观察到的端粒长度二态性的双峰分布,这一特征在 DFT1 中丢失。通过长期细胞培养,我们观察到端粒长度随时间逐渐均匀化。我们预测 DFT1 中也发生了类似的端粒长度均匀化,并且由于端粒长度的维持,DFT2 不太可能发生进一步的重大重排。

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