DNA copy number evolution in Drosophila cell lines.
DNA copy number evolution in Drosophila cell lines.
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DOI：
10.1186/gb-2014-15-8-r70
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发表时间：
2014-08-28
期刊：
影响因子：
12.3
通讯作者：
MacAlpine D
中科院分区：
文献类型：
--
作者：
Lee H;McManus CJ;Cho DY;Eaton M;Renda F;Somma MP;Cherbas L;May G;Powell S;Zhang D;Zhan L;Resch A;Andrews J;Celniker SE;Cherbas P;Przytycka TM;Gatti M;Oliver B;Graveley B;MacAlpine D
由于拷贝数变化而导致基因不平衡的基因组结构重排在生物体水平上通常是有害的，但在永生化细胞系和肿瘤中很常见，它们可能对细胞有利。为了探索果蝇基因组拷贝数变化的生物学后果，我们对 19 个组织培养细胞系的基因组进行了重新测序并生成了 RNA 测序图谱。我们的工作揭示了所有细胞系中的显着重复和缺失。我们发现了三行证据，表明拷贝数的变化是由于组织培养过程中的选择造成的。首先，我们发现拷贝数与维持蛋白质复合物和生化途径中的化学计量平衡相关，这与基因平衡假说一致。其次，虽然大多数拷贝数变化是细胞系特异性的，但我们发现了许多独立细胞系共有的一些拷贝数变化。其中包括 PDGF/VEGF 受体拷贝数的急剧复发（该受体在许多癌细胞中也过度表达）和 bantam（一种抗凋亡 miRNA）。第三，即使当品系之间的拷贝数变化似乎截然不同时，也有强有力的证据表明它们支持共同的表型结果。例如，我们发现原癌基因在一种细胞系（S2-DRSC）中代表性过高，而抑癌基因在另一种细胞系（Kc167）中代表性不足。我们的研究说明了基因组结构的变化如何有助于体外细胞系的选择。这对其他细胞水平的自然选择进程（包括肿瘤发生）具有影响。本文的在线版本 (doi:10.1186/gb-2014-15-8-r70) 包含补充材料，可供授权用户使用。
Structural rearrangements of the genome resulting in genic imbalance due to copy number change are often deleterious at the organismal level, but are common in immortalized cell lines and tumors, where they may be an advantage to cells. In order to explore the biological consequences of copy number changes in the Drosophila genome, we resequenced the genomes of 19 tissue-culture cell lines and generated RNA-Seq profiles. Our work revealed dramatic duplications and deletions in all cell lines. We found three lines of evidence indicating that copy number changes were due to selection during tissue culture. First, we found that copy numbers correlated to maintain stoichiometric balance in protein complexes and biochemical pathways, consistent with the gene balance hypothesis. Second, while most copy number changes were cell line-specific, we identified some copy number changes shared by many of the independent cell lines. These included dramatic recurrence of increased copy number of the PDGF/VEGF receptor, which is also over-expressed in many cancer cells, and of bantam, an anti-apoptosis miRNA. Third, even when copy number changes seemed distinct between lines, there was strong evidence that they supported a common phenotypic outcome. For example, we found that proto-oncogenes were over-represented in one cell line (S2-DRSC), whereas tumor suppressor genes were under-represented in another (Kc167). Our study illustrates how genome structure changes may contribute to selection of cell lines in vitro. This has implications for other cell-level natural selection progressions, including tumorigenesis. The online version of this article (doi:10.1186/gb-2014-15-8-r70) contains supplementary material, which is available to authorized users.
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影响因子：
64.8
作者：
通讯作者：
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DOI：
10.1093/bioinformatics/btr670
发表时间：
2012-02-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Boeva V;Popova T;Bleakley K;Chiche P;Cappo J;Schleiermacher G;Janoueix-Lerosey I;Delattre O;Barillot E
通讯作者：
Barillot E
影响因子：
64.5
作者：
Bashaw, GJ;Baker, BS
通讯作者：
Baker, BS
模因套件：用于发现和搜索的工具。
影响因子：
14.9
作者：
Bailey TL;Boden M;Buske FA;Frith M;Grant CE;Clementi L;Ren J;Li WW;Noble WS
通讯作者：
Noble WS
影响因子：
64.8
作者：
通讯作者：
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