Telomere Roles in Fungal Genome Evolution

这个项目将研究端粒的作用，形成染色体末端的DNA序列，在染色体进化和制造新基因中发挥作用。该项目将研究丝状真菌Magnaporthe的染色体末端，Magnaporthe是水稻和小麦植物的毁灭性病原体。在控制真菌与宿主植物相互作用的20多个已知基因中，至少有50%被发现靠近端粒。长期以来，这些基因如何（以及为什么）到达染色体末端一直是一个谜。最近的研究表明，M。染色体末端以异常高的频率进行重排，这可能导致染色体末端的内部序列的捕获和复制。这反过来又导致以前的亚端粒序列被转移到染色体内部。该项目将使用DNA测序和相关数据分析方法来验证端粒动力学是染色体进化的主要驱动力的假设。该项目主要涉及DNA测序和相关的数据分析技术（生物信息学）。具有生物学和计算机科学相关交叉培训的个人很少，来自这两个领域的个人之间的合作受到他们的培训和技能差异的挑战。认识到国家对具有双领域专业知识的个人的需求，本项目的大部分目标将通过来自肯塔基州大学，北肯塔基州大学，东肯塔基州大学和西肯塔基州大学，尽管对端粒生物学和相关染色体区域（亚端粒）在细胞生物学、生物体适应和进化中的重要性有着浓厚的兴趣，但由于在基因组组装中的代表性差，染色体末端的组织及其动态仍然知之甚少。驱动该项目的中心假设是端粒区域是真菌基因组进化的主要工厂，从而端粒危机的反复发作为原材料募集提供燃料，并且端粒拯救途径用于产生新序列。长期以来，人们一直认为真菌基因组可能是通过这种“适应性端粒失效”（ATF）进化的，但到目前为止，还没有发现任何例子。该项目将大大扩展对真菌基因组结构的认识，并揭示ATF对基因组组织和进化的全面影响。此外，怀疑亚端粒区域中核苷酸取代/插入缺失多态性的增加速率可进一步加速末端捕获序列的新功能化。该项目将测试与这些假设相关的一些预测，同时寻求更好地理解亚端粒内部基因组序列交换，因为它涉及真菌基因组结构和宿主适应。具体目标包括：1.为主要宿主特异性形式的M产生端到端基因组组装。分析和表征亚末端染色体区域的结构和基因多样性。2.评估端粒动力学对M.通过识别和表征前端粒的内化遗迹来研究基因组进化; 3.检查自发或实验诱导的端粒危机事件后的基因组重组;和4.通过促进生物学家和计算机科学家之间合作的“小型”本科生研究项目实现项目目标。

This project will examine the roles that telomeres, the DNA sequences that form the ends of chromosomes, play in chromosome evolution and in making new genes. The project will study chromosome ends in the filamentous fungus Magnaporthe oryzae - a devastating pathogen of rice and wheat plants. Of the more than 20 known genes that control fungus interactions with the host plants, at least 50% are found close to the telomeres. It has long been a puzzle as to how (and why) these genes find their ways to the chromosome ends. Recent work has shown that the M. oryzae chromosome ends undergo rearrangements at spectacularly high frequencies and this can lead to the capture and duplication of internal sequences at the chromosome ends. This, in turn, causes the formerly subtelomeric sequences to be relegated to the chromosome interior. This project will use DNA sequencing and related data analysis methods to test the hypothesis that telomere dynamics is a major driver of chromosome evolution. This project largely involves DNA sequencing and associated data analysis techniques (bioinformatics). Individuals with the relevant cross-training in biology and computer science are rare and collaborations between individuals from the two domains are challenged by differences in their training and skills. Recognizing a national need for individuals with dual domain expertise, most of the objectives for this project will be completed through research experiences for teams of biology and computer science undergraduates from the partner institutions of the Univ. of Kentucky, Northern Kentucky Univ., Eastern Kentucky Univ. and Western Kentucky Univ., with specific efforts being made to enhance participation for student populations traditionally underrepresented in STEM research.Despite intense interest in telomere biology and the importance of the associated chromosome regions (subtelomeres) in cellular biology, organismal adaptation and evolution, the organization of chromosome ends and their dynamics is poorly understood due to poor representation in genome assemblies. The central hypothesis driving this project is that the telomere regions are the main factories of fungal genome evolution, whereby recurrent bouts of telomere crisis provide the fuel for raw materials recruitment and telomere rescue pathways act to generate novel sequences. It has long been proposed that fungal genomes might evolve through such "Adaptive Telomere Failure" (ATF) but, until now, no examples had been identified. This project will greatly expand knowledge on fungal genome structure and reveal the full impact of ATF on genome organization and evolution. Additionally, it is suspected that enhanced rates of nucleotide substitution/indel polymorphism in the subtelomeric regions may further accelerate the neo-functionalization of terminally captured sequences. This project will test a number of predictions related to these hypotheses, while seeking to gain an improved understanding of subtelomere-internal genome sequence exchange, as it relates to fungal genome structure and host adaptation. Specific objectives include: 1. Generate end-to-end genome assemblies for the main host-specialized forms of M. oryzae and characterize the structural and genic diversity of the subterminal chromosome regions. 2. Assess the impact of telomere dynamics on M. oryzae genome evolution by identifying and characterizing internalized relics of former telomeres; 3. Examine genome reorganization following spontaneous or experimentally-induced telomere crisis events; and 4. Accomplish project objectives through "bite-sized" undergraduate research projects that foster collaboration between biologists and computer scientists.