Molecular Mechanisms of Genome Duplication

基因组复制的分子机制

• 批准号: 6681551
• 负责人: ZENGJIAN JEFFREY CHEN
• 金额: $ 26.63万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6681551
• 关键词: Arabidopsis; DNA damage; DNA methylation; DNA repair; chemical stability; chromatin; chromosome translocation; clinical research; gene duplication; gene induction /repression; genome; molecular genetics; polyploidy

DESCRIPTION (provided by applicant): Genome duplication is an important speciation mechanism for all eukaryotes, especially animals and plants. On one hand, genome duplication provides additional genetic material for adaptive evolution and natural variation; on the other, genome duplication results in chromosome imbalance and intrinsic instability of polyploids and aneuploids. Moreover, increased gene and genome dosage may cause abnormal cell cycle control and disease syndromes. Thus, to take advantage of novel variation and fitness but avoid deleterious effects, polyploid cells must establish a new relationship between alien cytoplasm and nuclei and reprogram expression patterns of orthologous and paralogous genes derived from their progenitors. Some duplicate genes must be silenced, whereas others may be instantly expressed or spatially and temporally regulated. Indeed, our recent studies indicate that genetic and epigenetic regulation is involved in reprogramming genome stability and gene expression in polyploids. Here we test hypotheses concerning fundamental biological and genetic consequences of genome duplication. We will determine how genome stability is maintained in newly formed polyploids. We will test if gene activation and silencing is stable or stochastic in natural and new polyploids. Changes in chromatin and DNA methylation status of candidate genes will be monitored when the silenced genes are reactivated. The hypothesis that orthologous genes are controlled independently of chromosomal location will be tested by determining if transgenes at ectopic locations are silenced. By silencing active orthologous genes, we will determine if silencing decisions are randomly made. We will test if RNA interference is involved in silencing endogenous redundant genes as it is in silencing transgenes and developmentally regulated genes. Furthermore, we will explore the role of alien cytoplasmic and nuclear compatibility in the evolutionary success of polyploids. Elucidating the molecular basis of genome stability and gene expression in recent and established polyploids will provide fundamental knowledge needed to understand mechanisms for natural variation and epigenetic phenomena important in medicine, such as X-chromosome inactivation, gametic imprinting, and disease syndromes.

描述（由申请人提供）：基因组复制是所有真核生物，尤其是动物和植物的重要物种形成机制。一方面，基因组复制为适应性进化和自然变异提供了额外的遗传物质；另一方面，基因组重复导致染色体失衡以及多倍体和非整倍体的内在不稳定性。此外，基因和基因组剂量的增加可能会导致细胞周期控制异常和疾病综合征。因此，为了利用新的变异和适应度但避免有害影响，多倍体细胞必须在外来细胞质和细胞核之间建立新的关系，并重新编程源自其祖细胞的直系同源和旁系同源基因的表达模式。一些重复基因必须被沉默，而其他基因可能会立即表达或在空间和时间上受到调节。事实上，我们最近的研究表明，遗传和表观遗传调控参与了多倍体基因组稳定性和基因表达的重编程。在这里，我们测试有关基因组复制的基本生物学和遗传后果的假设。我们将确定如何在新形成的多倍体中维持基因组稳定性。我们将测试天然多倍体和新多倍体中基因激活和沉默是否稳定或随机。当沉默的基因重新激活时，将监测候选基因的染色质和 DNA 甲基化状态的变化。通过确定异位位置的转基因是否被沉默，可以检验直系同源基因不受染色体位置控制的假设。通过沉默活跃的直系同源基因，我们将确定沉默决定是否是随机做出的。我们将测试 RNA 干扰是否参与沉默内源冗余基因，就像沉默转基因和发育调控基因一样。此外，我们将探讨外来细胞质和核相容性在多倍体进化成功中的作用。阐明最近和已建立的多倍体中基因组稳定性和基因表达的分子基础，将为理解医学上重要的自然变异和表观遗传现象（例如 X 染色体失活、配子印记和疾病综合征）的机制提供所需的基础知识。