Molecular Mechanisms of Genome Duplication

描述(申请人提供)：基因组复制是所有真核生物，特别是动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，基因组复制导致染色体失衡和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症状。因此，为了利用新的变异和适应性，同时避免有害影响，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，并重新编程来自其祖先的同源和近源基因的表达模式。一些重复的基因必须沉默，而另一些可能是即时表达的，或者在空间和时间上受到调控。事实上，我们最近的研究表明，遗传和表观遗传调节参与了重新编程基因组的稳定性和多倍体中的基因表达。在这里，我们测试关于基因组复制的基本生物学和遗传学后果的假设。我们将确定如何在新形成的多倍体中保持基因组的稳定性。我们将测试基因的激活和沉默在自然多倍体和新的多倍体中是稳定的还是随机的。当沉默的基因重新激活时，将监测候选基因染色质和DNA甲基化状态的变化。将通过确定异位基因是否被沉默来检验同源基因独立于染色体位置受到控制的假设。通过沉默活跃的同源基因，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性冗余基因，就像它沉默转基因和发育调节基因一样。此外，我们还将探讨异源细胞质和核亲和性在多倍体进化成功中的作用。阐明基因组稳定性的分子基础和最近建立的多倍体中的基因表达将提供必要的基础知识，以了解自然变异和医学上重要的表观遗传现象的机制，如X染色体失活、配子印记和疾病综合征。

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.