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.

项目总结