Coevolutionary Dynamics and Gene Exchange Between Nucleo-Cytoplasmic Large DNA Viruses and Eukaryotes

核质大DNA病毒与真核生物之间的协同进化动力学和基因交换

• 批准号: 10684095
• 负责人: Frank O'Neill Aylward
• 金额: $ 36.91万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-16 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10684095
• 关键词: Algae; Animals; Asfarviridae; Back; Biological Models; Carbon; Chlamydomonas reinhardtii; Complement; Complex; Cytoskeleton; DNA Virus Infections; DNA Viruses; Data; Elements; Eukaryota; Evolution; Family; Family Study; Foundations; Gene Exchanges; Genes; Genetic; Genome; Green Algae; Human; Inhibition of Apoptosis; Interdisciplinary Study; Iridoviridae; Metabolism; Modeling; Molecular; Nature; Nutrient; Phycodnaviridae; Plants; Play; Poxviridae; Process; Public Health; Recording of previous events; Research; Role; Shapes; Structure; System; Translations; Vertebrates; Viral; Viral Genome; Virus; Work; experimental analysis; immunoregulation; insight; mimicry; molecular dynamics; pathogen; programs; tool; virus host interaction

Project Summary Nucleo-Cytoplasmic Large DNA Viruses (NCLDVs) are a group of eukaryotic pathogens that includes the largest and most complex viruses known. This group encompasses well-studied families that infect vertebrates, such as Poxviridae, Asfarviridae, and Iridoviridae, as well as families that infect diverse unicellular eukaryotes, such as Mimiviridae, Phycodnaviridae, and Marseilleviridae. NCLDVs are an ancient lineage that have co-evolved with eukaryotes for many millions of years, and the genomes of both viruses and their hosts contain myriad signatures of past and present interactions. NCLDV genomes encode an impressive complement of host-derived genes ─ often referred to as viral mimicry genes ─ that are involved in numerous processes such as immunoregulation, apoptosis inhibition, central carbon metabolism, cytoskeletal structure, nutrient transport, and translation. The evolutionary history of most of these genes is unclear beyond their original acquisition from cellular lineages, and the processes that give rise to mimicry are therefore largely unknown. Eukaryotic genomes also bear testament to their interactions with these viruses, and recent work has shown that endogenized NCLDVs are surprisingly common across a wide range of eukaryotic hosts, including animals and plants. These endogenous viral elements range from large >1 Mbp loci ─ termed Giant Endogenous Viral Elements, or GEVEs ─ to smaller loci containing only a few genes that can be traced back to NCLDV. My group has identified GEVEs across a range of green algae, and I have preliminary data demonstrating that recently-endogenized NCLDVs are present in the genomes of several strains of the model green alga Chlamydomonas reinhardtii. These and other recent findings demonstrate that both historical and contemporary gene exchange between NCLDVs and eukaryotes plays a large role in the genome evolution of both groups, but we currently lack a quantitative framework or model system for evaluating the nature and extent of these dynamics. Here I propose several computational and wet-lab research directions aimed at evaluating the evolutionary dynamics of both host- derived mimicry genes in NCLDVs as well as the NCLDV-derived loci in eukaryotic genomes. I also propose to develop C. reinhardtii as a model to facilitate in-depth experimental analysis of host-virus interactions and evaluate the consequences of NCLDV endogenization in detail. Due to the existing genetic tools that have been developed for C. reinhardtii, establishment of this alga as a new model for NCLDV-host interactions would be a transformative advance that would enable detailed experimental analyses that are currently not possible in other virus-host experimental systems. Overall, these research themes form the basis of an interdisciplinary research program focused on disentangling the evolutionary and molecular dynamics of NCLDV-host interactions. This work will establish a quantitative framework for understanding the deeply intertwined coevolution between NCLDVs and their hosts while also developing a new model system for detailed molecular experimentation.

项目概要 核胞质大 DNA 病毒 (NCLDV) 是一组真核病原体，其中包括最大的 以及已知的最复杂的病毒。该群体包括经过充分研究的感染脊椎动物的家族，例如 如痘病毒科、阿斯法病毒科和虹彩病毒科，以及感染多种单细胞真核生物的科，例如 如拟菌病毒科、藻DNA病毒科和马赛病毒科。 NCLDV 是一个共同进化的古老谱系 与真核生物存在了数百万年的历史，病毒及其宿主的基因组都包含无数的 过去和现在互动的签名。 NCLDV 基因组编码大量源自宿主的 基因（通常被称为病毒拟态基因）参与许多过程，例如 免疫调节、细胞凋亡抑制、中心碳代谢、细胞骨架结构、营养物质运输和 翻译。大多数这些基因的进化历史除了它们最初获得的以外尚不清楚。 因此，细胞谱系以及产生拟态的过程在很大程度上是未知的。真核基因组 也证明了它们与这些病毒的相互作用，最近的工作表明，内源性 令人惊讶的是，NCLDV 在包括动物和植物在内的多种真核宿主中都很常见。这些 内源性病毒元件的范围从大于 1 Mbp 的大型位点 ─ 称为巨型内源性病毒元件，或 GEVE ─ 较小的基因座，仅包含少数可追溯到 NCLDV 的基因。我的团队已确定 GEVE 跨越一系列绿藻，我有初步数据表明最近内源化的 NCLDV 存在于几种模型绿藻莱茵衣藻菌株的基因组中。这些和 最近的其他研究结果表明，NCLDV 和 NCLDV 之间的历史和当代基因交换 真核生物在这两个群体的基因组进化中都发挥着重要作用，但我们目前缺乏定量的证据 用于评估这些动态的性质和程度的框架或模型系统。这里我推荐几个 计算和湿实验室研究方向旨在评估宿主的进化动力学 NCLDV 中衍生的拟态基因以及真核基因组中 NCLDV 衍生的基因座。我也提议 开发莱茵衣藻作为模型，以促进宿主与病毒相互作用的深入实验分析， 详细评估 NCLDV 内源化的后果。由于现有的遗传工具 为 C. Reinhardtii 开发的藻类，将这种藻类建立为 NCLDV-宿主相互作用的新模型将是一个 革命性的进步将使详细的实验分析成为可能，而这在其他领域目前是不可能的 病毒宿主实验系统。总体而言，这些研究主题构成了跨学科研究的基础 该计划的重点是解开 NCLDV-宿主相互作用的进化和分子动力学。这 这项工作将建立一个定量框架来理解之间深度交织的共同进化 NCLDV 及其宿主同时还开发了用于详细分子实验的新模型系统。