Collaborative Research: Impact of a novel retrotransposon expansion on centromere function

合作研究：新型逆转录转座子扩展对着丝粒功能的影响

• 批准号: 1613806
• 负责人: Rachel O'Neill
• 金额: $ 56.38万
• 依托单位: University of Connecticut
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-15 至 2020-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1613806&HistoricalAwards=false
• 关键词: Collaborative; Research; Impact; novel; retrotransposon

Centromeres are DNA regions that ensure the correct separation of chromosomes during a cell's reproduction, and are fundamental to genome evolution. However, due to the highly repetitive nature of DNA present in centromeres, further studies in identifying the make-up of this portion of DNA have been limited. In response to the roadblocks caused by the limited amount of research in this area, this project aims to advance our knowledge of centromere biology and evolution. This research will support outreach activities focused on the biology of gibbons, a critically endangered group of primates. As the main threats for these species are from human activities, a large part of the outreach effort for this work seeks to increase awareness of the precarious state of this species. Current conservation efforts, encompassing different venues, include informal seminars to the public and collaborations with primate centers and museums. In addition, this project will promote education through training of postdoctoral fellows, graduate students, undergraduate and local high school programs by providing experiential learning and exposure to modern technologies and training workshops.While expansions of DNA within centromeres are known for many species, most centromeres are stable over evolutionary time and relatively uniform across all centromeres in one genome. Decoupling equilibration events across chromosomes from the initial seeding events specific to a subset of chromosomes has not been possible in most model systems. This project capitalizes on the recently discovered centromeric expansion of a selfish element, the LAVA retroelement, in a subset of chromosomes in one gibbon genus (Hoolock). This project will build upon foundational discoveries in gibbon centromeres, the newly released gibbon genome sequence and novel genomics approaches for studying complex, repeat-rich regions. This project will test the hypothesis that both LAVA and neighboring satellite DNA bind inner kinetochore proteins, implicating genetic conflict in the seeding and expansion at centromeres. Second, based on observations that the Hoolock centromere structure is similar to that found in marsupials and plants, this project will include analyses of transcripts from centromeric repeats to determine whether transcription from centromere retroelements is associated with young centromere restructuring or with subsequent stabilization. Finally, this research will incorporate emerging next-generation sequencing technologies to assemble Hoolock centromeres from single chromosomes. Collectively, these aims will determine the impact of the organization and function of repeats among newly seeded centromeres and stabilized centromeres within one karyotype.This project is funded by the Genetic Mechanisms Program in the Division of Molecular and Cellular Biosciences.

着丝粒是确保细胞繁殖过程中染色体正确分离的DNA区域，是基因组进化的基础。然而，由于着丝粒中存在的DNA的高度重复性质，进一步的研究在识别这部分DNA的组成方面一直受到限制。为了应对这一领域有限的研究造成的障碍，该项目旨在促进我们对着丝粒生物学和进化的了解。这项研究将支持以长臂猿生物学为重点的推广活动，长臂猿是一种极度濒危的灵长类动物。由于这些物种面临的主要威胁来自人类活动，这项工作的很大一部分推广工作是为了提高人们对该物种岌岌可危状态的认识。目前的保护工作包括不同的场所，包括面向公众的非正式研讨会，以及与灵长类中心和博物馆的合作。此外，该项目将通过培训博士后研究员、研究生、本科生和当地高中项目来促进教育，通过提供体验式学习以及接触现代技术和培训车间。虽然着丝粒内DNA的扩展在许多物种中是已知的，但大多数着丝粒在进化过程中是稳定的，并且在一个基因组中的所有着丝粒上相对一致。在大多数模型系统中，将染色体上的平衡事件与特定于染色体子集的初始播种事件去耦合是不可能的。这个项目利用了最近发现的一个长臂猿属(Hoolock)染色体子集中一种自私分子--熔岩反转录分子的着丝粒扩展。该项目将建立在长臂猿着丝粒的基础性发现、新发布的长臂猿基因组序列和研究复杂、富含重复序列的区域的新基因组学方法的基础上。这个项目将检验这样的假设，即熔岩和邻近的卫星DNA都与内部动粒蛋白结合，这意味着在着丝粒的播种和扩张过程中存在遗传冲突。其次，基于Hoolock着丝粒结构与在有袋类和植物中发现的结构相似的观察，该项目将包括对着丝粒重复序列的转录进行分析，以确定着丝粒逆转录元件的转录是否与年轻的着丝粒重组或随后的稳定有关。最后，这项研究将结合新兴的下一代测序技术，从单个染色体组装Hoolock着丝粒。总的来说，这些目标将决定一个核型内新种子着丝粒和稳定着丝粒之间重复序列的组织和功能的影响。该项目由分子和细胞生物科学部门的遗传机制计划资助。