The evolutionary and functional genomics of satellite DNA

项目总结 真核生物基因组包含我们目前知之甚少的重复非编码序列阵列 关于卫星DNA。通常发现在着丝粒、端粒附近和Y染色体上，卫星DNA 可以包含超过50%的一些真核基因组。众所周知，它们会按顺序快速变化，并且 基因组位置，这可能导致密切相关物种之间的遗传不亲和性。这个 卫星DNA的错误调控会对基因组的稳定和癌症的形成产生严重的后果。 尽管我们是基因组中无处不在的一部分，并具有重要的功能后果，但我们知道的很少 关于卫星DNA。缺乏研究重复序列的遗传、基因组和分子工具 阻碍了理解卫星DNA进化和功能的进展。例如，卫星DNA 在测序和组装方面尤其具有挑战性。新一代测序技术的最新进展 技术可以绕过其中的一些问题。该方案集基因组、分子和细胞学于一体。 方法研究果蝇基因组中卫星DNA的进化和功能基因组学。少年派有 发展了新的基因组和细胞学方法来研究进化动力学、基因组结构和 以前所未有的分辨率表达卫星DNA。PI将使用这些方法来研究 卫星DNA序列、丰度和组织随进化时间的变化并决定进化 造成这些变化的力量。该提案旨在开发卫星DNA的综合模型 考虑不同类型的自然选择的进化论 卫星DNA。目前对卫星DNA的功能知之甚少：卫星的精确遗传操作 过去，由于缺乏独特的目标部位，采用特定部位的DNA方法是不可能的。这个 这项提案中开发的新基因组方法为发现侧翼的独特位点提供了机会 可作为基因组编辑技术目标的卫星DNA。该提案将创造出准确的 果蝇基因组中卫星DNA的缺失以检验关于这一调控的特定假设， 卫星DNA的适应度效应和自私遗传行为。这项提议还将使用新的分子遗传 操纵胚系中卫星DNA表达的技术，以提出关于其 染色体分离和染色质组织的功能。这些实验将会有广泛的应用 不仅对基因组进化的影响，而且对理解卫星DNA在癌症中的调节也有意义 和衰老。

Project summary Eukaryotic genomes contain arrays of tandemly repeated non-coding sequences that we currently know little about—satellite DNAs. Typically found near centromeres, telomeres and on Y chromosomes, satellite DNAs can comprise over 50% of some eukaryotic genomes. They are known to change rapidly in sequence and genomic location, which can cause genetic incompatibilities between closely related species. The misregulation of satellite DNA can have serious consequences for genomic stability and cancer formation. Despite being a ubiquitous part of genomes and having important functional consequences, we know little about satellite DNA. The lack of genetic, genomic and molecular tools to study tandemly repeated sequences has stymied progress towards understanding satellite DNA evolution and function. For example, satellite DNAs are particularly challenging to sequence and assemble. Recent developments in next-generation sequencing technologies circumvent some of these problems. This proposal integrates genomic, molecular and cytological methods to study the evolutionary and functional genomics of satellite DNA in Drosophila genomes. The PI has developed new genomic and cytological methods to study the evolutionary dynamics, genomic structure and expression of satellite DNA with unprecedented resolution. The PI will use these methods to study changes in satellite DNA sequence, abundance and organization over evolutionary time and to determine the evolutionary forces responsible for these changes. This proposal aims to develop comprehensive models of satellite DNA evolution that take into consideration different types of natural selection based on the functional aspects of satellite DNAs. Little is currently known of satellite DNA function: the precise genetic manipulation of satellite DNAs with site-specific approaches had not been possible in the past due to a lack of unique target sites. The new genomic methods developed in this proposal provide an opportunity to discover unique sites flanking satellite DNAs that may serve as targets for genome editing techniques. The proposal will create precise genomic deletions of satellite DNA in Drosophila melanogaster to test specific hypotheses about the regulation, fitness effects and selfish genetic behavior of satellite DNA. This proposal will also use new molecular genetic techniques to manipulate the expression of satellite DNAs in the germline to ask questions about their functions in chromosome segregation and chromatin organization. These experiments will have broad implications not only for genome evolution, but also for understanding the regulation of satellite DNA in cancer and aging.