Effects of aneuploidy on genome structure, expression, and interphase organization in Arabidopsis thaliana.
Effects of aneuploidy on genome structure, expression, and interphase organization in Arabidopsis thaliana.
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DOI：
10.1371/journal.pgen.1000226
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发表时间：
2008-10
期刊：
影响因子：
4.5
通讯作者：
Matzke, Antonius J. M.
中科院分区：
文献类型：
--
作者：
Huettel, Bruno;Kreil, David P.;Matzke, Marjori;Matzke, Antonius J. M.
非整倍体是指正常染色体组中单个染色体的丢失和/或获得。由此产生的基因剂量失衡对表型有明显的影响，如非整倍体综合征，包括人类的唐氏综合征，以及高度非整倍体的人类实体瘤细胞。尽管非整倍体的表型表现通常是明显的，但关于不平衡染色体组的结构、表达和间期组织的潜在变化的信息仍然很少。植物一般比动物更耐受非整倍体，通过秋水仙素处理和育种策略，有可能获得具有不同染色体数目的近交兄弟植物。这种可能性与拟南芥可用的遗传和基因组学工具相结合，为系统地评估特定染色体数量异常的分子和细胞学后果提供了强有力的手段。在这里，我们报告了5号染色体呈三倍体存在的拟南芥植株的世代。我们比较了正常二倍体和5号染色体三体的全球转录图谱，并使用阵列比较基因组杂交评估了基因组的完整性。我们使用活细胞成像来确定三体和三倍体植物中转基因编码的荧光标记在5号染色体上的间期3D排列。结果表明，5三体干扰了整个基因组的基因表达，并支持5号染色体截短拷贝的产生和/或保留。虽然5三体不会严重扭曲5号染色体上荧光标记位点的间期排列，但它可能在一定程度上增强转基因等位基因之间的联系。我们的分析揭示了在非整倍体中可能发生的复杂的基因组变化，并强调了使用多种实验方法来研究染色体数量变化如何导致异常表型和进行性基因组不稳定性的重要性。大多数植物和动物在正常染色体集中每个染色体都有两个拷贝。由个体染色体(非整倍体)的获得或丢失引起的不平衡的数目变化通常会产生有害的后果。例如，人类的唐氏综合症是由21号染色体的一个额外(三重)拷贝引起的。人类肿瘤细胞通常在染色体数目和结构上表现出大量的变化。关于染色体数目的变化如何影响基因活性和染色体完整性，从而扰乱生理和发育，人们知之甚少。我们已经使用模式植物A.thaliana来研究5号染色体的三倍体如何影响基因表达、染色体结构和染色体在核中的包装。结果表明，额外的5号染色体的存在有多种影响：(1)基因表达发生实质性变化，主要是在三倍体5号染色体上，但也在四条非三倍体染色体上；(2)在存在两个正常副本的情况下，5号染色体的断裂衍生品可以保留；(3)三倍体5号染色体的两个副本可能显示出略有增强的相互关联倾向，可能是为了在空间上补偿染色体失衡。非整倍体的有害影响可能是由于基因表达、染色体结构和排列同时发生变化。
Aneuploidy refers to losses and/or gains of individual chromosomes from the normal chromosome set. The resulting gene dosage imbalance has a noticeable affect on the phenotype, as illustrated by aneuploid syndromes, including Down syndrome in humans, and by human solid tumor cells, which are highly aneuploid. Although the phenotypic manifestations of aneuploidy are usually apparent, information about the underlying alterations in structure, expression, and interphase organization of unbalanced chromosome sets is still sparse. Plants generally tolerate aneuploidy better than animals, and, through colchicine treatment and breeding strategies, it is possible to obtain inbred sibling plants with different numbers of chromosomes. This possibility, combined with the genetic and genomics tools available for Arabidopsis thaliana, provides a powerful means to assess systematically the molecular and cytological consequences of aberrant numbers of specific chromosomes. Here, we report on the generation of Arabidopsis plants in which chromosome 5 is present in triplicate. We compare the global transcript profiles of normal diploids and chromosome 5 trisomics, and assess genome integrity using array comparative genome hybridization. We use live cell imaging to determine the interphase 3D arrangement of transgene-encoded fluorescent tags on chromosome 5 in trisomic and triploid plants. The results indicate that trisomy 5 disrupts gene expression throughout the genome and supports the production and/or retention of truncated copies of chromosome 5. Although trisomy 5 does not grossly distort the interphase arrangement of fluorescent-tagged sites on chromosome 5, it may somewhat enhance associations between transgene alleles. Our analysis reveals the complex genomic changes that can occur in aneuploids and underscores the importance of using multiple experimental approaches to investigate how chromosome numerical changes condition abnormal phenotypes and progressive genome instability. Most plants and animals have two copies of each chromosome in the normal chromosome set. Unbalanced numerical changes resulting from gains or losses of individual chromosomes (aneuploidy) usually have deleterious consequences. For example, Down syndrome in humans is caused by an extra (triplicate) copy of chromosome 21. Human tumor cells usually display numerous alterations in chromosome number and structure. Little is known about how changes in chromosome number influence gene activity and chromosome integrity, thereby perturbing physiology and development. We have used the model plant A. thaliana to study how triplication of chromosome 5 affects gene expression, chromosome structure, and chromosome packaging in the nucleus. The results indicate that the presence of an extra chromosome 5 has multiple effects: (1) substantial changes in gene expression occur, primarily on the triplicated chromosome 5 but also on the four non-triplicated chromosomes; (2) broken derivatives of chromosome 5 can be retained in the presence of two normal copies; and (3) two copies of the triplicated chromosome 5 may show a slightly enhanced tendency to associate with each other, perhaps to spatially compensate for the chromosome imbalance. The detrimental effects of aneuploidy are likely due to concurrent changes in gene expression, chromosome structure, and arrangement.
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