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.

项目摘要 核质大DNA病毒（Nucleo-Cytoplasmic Large DNA Virus，NCLDVs）是一组真核生物病原体， 最复杂的病毒这一组包括研究充分的家庭，感染脊椎动物，如 如痘病毒科、Asfarviridae和虹彩病毒科，以及感染不同单细胞真核生物的科，如 如微病毒科、藻DNA病毒科和马赛病毒科。NCLDV是一个古老的谱系， 与真核生物有数百万年的关系，病毒和它们的宿主的基因组都含有无数的 过去和现在互动的特征NCLDV基因组编码一个令人印象深刻的宿主来源的互补序列， 基因--通常被称为病毒模仿基因--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、营养转运和 翻译.大多数这些基因的进化历史是不清楚的，超出了他们最初的收购， 因此，细胞谱系和产生拟态的过程在很大程度上是未知的。真核生物基因组 也证明了它们与这些病毒的相互作用，最近的研究表明，内源性 NCLDV在包括动物和植物在内的广泛的真核宿主中令人惊讶地常见。这些 内源性病毒元件包括大于1 Mbp的大基因座，称为巨大内源性病毒元件，或GEVE ─到只含有几个基因的较小的基因座，可以追溯到NCLDV。我的小组已经确定了GEVE 在一系列绿色藻类中，我有初步的数据表明，最近内源化的NCLDVs 存在于模式绿色衣藻莱茵衣藻的几个菌株的基因组中。这些和 其他最近的发现表明，历史和当代NCLDVs之间的基因交换， 真核生物在这两个群体的基因组进化中起着重要作用，但我们目前缺乏定量的 评估这些动态的性质和程度的框架或模型系统。在这里，我提出几个 计算和湿实验室的研究方向，旨在评估两个主机的进化动力学， NCLDV中的NCLDV衍生的拟态基因以及真核基因组中的NCLDV衍生的基因座。我亦建议 发展C. reinhardtii作为模型，以促进宿主-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，建立这种新的模式，为NCLDV-宿主相互作用将是一个 这是一个变革性的进步，将使详细的实验分析，目前不可能在其他 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，用于理解 NCLDV和它们的宿主，同时也为详细的分子实验开发了一个新的模型系统。