Genetic basis for dosage sensitivity in Arabidopsis thaliana.
Genetic basis for dosage sensitivity in Arabidopsis thaliana.
复制标题
DOI：
10.1371/journal.pgen.0030070
复制
发表时间：
2007-04-27
期刊：
影响因子：
4.5
通讯作者：
Comai L
中科院分区：
文献类型：
--
作者：
Henry IM;Dilkes BP;Comai L
非整倍性，即特定染色体类型的相对过量或缺乏，会导致基因剂量不平衡。植物可以产生可存活且可育的非整倍体个体，而大多数动物非整倍体是无法存活或发育异常的。拟南芥三倍体产生的非整倍体后代群构成了研究剂量敏感性和非整倍体综合征的机制的绝佳模型。事实上，基因型改变了这些群体中非整倍体类型的频率。源自三倍体杂种的重组自交系分离成二倍体和四倍体个体。在这些重组自交系中，我们称之为对剂量不平衡敏感（SDI）的单个位点仅在四倍体亚群中表现出分离扭曲。定量基因分型的最新进展现在允许对非整倍体群体进行分子核型分析和遗传分析。在这项研究中，我们研究了 SDI 倍性特异性畸变的原因。三倍体杂交产生的非整倍体群中的等位基因频率被扭曲。我们开发了一种简单的非整倍体致死性定量测量方法，并使用这种测量方法证明，在面临最强生存力选择的非整倍体中畸变最大。当三倍体与整倍体杂交时，缺乏严重非整倍体的后代在 SDI 时没有表现出畸变。非整倍体群中 SDI 的遗传特征确定了一种控制非整倍体生存的机制，可能是通过缓冲剂量不平衡的影响。因此，SDI 可以增加保留基因组重排（例如片段重复）的可能性。此外，在三倍体可育的物种中，非整倍体的存活将促进二倍体和四倍体群体之间的基因通过三倍体桥流动并防止多倍体物种形成。我们的结果表明，使用定量基因分型方法现在可以对影响包含倍性和染色体数目变异的群体中性状的基因座进行位置克隆。每个真核基因组被细分为特定数量的染色体类型，这些染色体类型又以特征数量的拷贝存在，通常所有染色体都相同。在非整倍性的情况下，不同染色体类型的拷贝数不同，破坏了它们的平衡及其编码因子的平衡。因此，非整倍性与发育缺陷和死亡有关。例如，大多数类型的人类非整倍体都是无法生存的：唐氏综合症是唯一与长期生存相容的常染色体非整倍体，是由非常小的21号染色体的三个拷贝而不是两个拷贝引起的。在植物中，非整倍体更常见且危害较小。这表明植物更容易忍受非整倍性的影响，并可用于研究它们。在这里，我们使用模式植物拟南芥来产生和研究非整倍体个体群体。通过比较遗传上不同的非整倍体群体，我们确定了与更大的非整倍体存活率相关的染色体区域。表征调节对染色体剂量和非整倍体存活变化的反应的遗传机制将有助于理解基因组组织如何影响生物过程以及为什么非整倍体会导致如此严重的发育缺陷。
Aneuploidy, the relative excess or deficiency of specific chromosome types, results in gene dosage imbalance. Plants can produce viable and fertile aneuploid individuals, while most animal aneuploids are inviable or developmentally abnormal. The swarms of aneuploid progeny produced by Arabidopsis triploids constitute an excellent model to investigate the mechanisms governing dosage sensitivity and aneuploid syndromes. Indeed, genotype alters the frequency of aneuploid types within these swarms. Recombinant inbred lines that were derived from a triploid hybrid segregated into diploid and tetraploid individuals. In these recombinant inbred lines, a single locus, which we call SENSITIVE TO DOSAGE IMBALANCE (SDI), exhibited segregation distortion in the tetraploid subpopulation only. Recent progress in quantitative genotyping now allows molecular karyotyping and genetic analysis of aneuploid populations. In this study, we investigated the causes of the ploidy-specific distortion at SDI. Allele frequency was distorted in the aneuploid swarms produced by the triploid hybrid. We developed a simple quantitative measure for aneuploidy lethality and using this measure demonstrated that distortion was greatest in the aneuploids facing the strongest viability selection. When triploids were crossed to euploids, the progeny, which lack severe aneuploids, exhibited no distortion at SDI. Genetic characterization of SDI in the aneuploid swarm identified a mechanism governing aneuploid survival, perhaps by buffering the effects of dosage imbalance. As such, SDI could increase the likelihood of retaining genomic rearrangements such as segmental duplications. Additionally, in species where triploids are fertile, aneuploid survival would facilitate gene flow between diploid and tetraploid populations via a triploid bridge and prevent polyploid speciation. Our results demonstrate that positional cloning of loci affecting traits in populations containing ploidy and chromosome number variants is now feasible using quantitative genotyping approaches. Each eukaryotic genome is subdivided into a specific number of chromosome types, which in turn are present in a characteristic number of copies, usually the same for all chromosomes. In the condition called aneuploidy, copy number differs among chromosome types, disrupting their balance and that of their encoded factors. As a result, aneuploidy is associated with developmental defects and death. For example, most types of human aneuploids are unviable: the only autosomal aneuploidy compatible with protracted survival, Down syndrome, is caused by the presence of three copies, instead of two, of the very small Chromosome 21. In plants, aneuploidy is more common and less deleterious. This suggests that plants can more easily tolerate the effects of aneuploidy and can be used to investigate them. Here, we used the model plant Arabidopsis thaliana to produce and investigate populations of aneuploid individuals. By comparing genetically distinct aneuploid populations, we identified a chromosomal region that is associated with greater aneuploid survival. Characterizing the genetic mechanism modulating the response to changes in chromosomal dosage and aneuploid survival will help understand how genome organization affects biological processes and why aneuploidy results in such severe developmental defects.
登录
查看更多内容
影响因子：
3.3
作者：
Henry, IM;Dilkes, BP;Comai, L
通讯作者：
Comai, L
影响因子：
4.4
作者：
BELL, CJ;ECKER, JR
通讯作者：
ECKER, JR
影响因子：
4.4
作者：
Mao, R;Zielke, CL;Pevsner, J
通讯作者：
Pevsner, J
影响因子：
3.1
作者：
Cervera, MT;Ruiz-García, L;Martínez-Zapater, JM
通讯作者：
Martínez-Zapater, JM
影响因子：
3.5
作者：
FitzPatrick, DR;Ramsay, J;Hastie, ND
通讯作者：
Hastie, ND