Experimental models of viral genome evolution

病毒基因组进化的实验模型

• 批准号: 7105709
• 负责人: JAMES J BULL
• 金额: $ 19.07万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7105709
• 关键词: bacteriophage T7; biotechnology; chromosome aberrations; directed evolution; environmental adaptation; evolution; gene deletion mutation; gene interaction; gene rearrangement; genetic mapping; genetic regulation; molecular biology; nucleic acid sequence; polymerase chain reaction; population genetics; site directed mutagenesis; virus genetics

DESCRIPTION (provided by applicant): This study will use the genome network as a framework for predicting evolution in a virus. The viral genome will be modified in simple ways by deleting or replacing a single gene, and the modified virus will be adapted to observe how it evolves in response to the modification. The general prediction is that changes which evolve in the modified virus will occur in the parts of the genome known to interact with the modified gene. The study will provide a direct test of this framework with experimental data. The virus used is the harmless bacteriophage T7, which offers a good model system for other viruses because much is already known about T7 molecular biology, a genome network can be assembled, and T7 grows only on a few strains of bacteria. The work will give useful insight to several questions and goals in public health and molecular epidemiology, as well as in basic biology: (i) the feasibility of engineering new genomes and creating recombinant vaccines safely; (ii) how well we can predict molecular evolution; (iii) whether genome interactions are conserved across related species; (iv) how to detect genetic signatures of evolution in engineered versus natural genomes.

描述（由申请人提供）：本研究将使用基因组网络作为预测病毒进化的框架。通过删除或替换单个基因，病毒基因组将被修改，修改后的病毒将适应观察它如何响应修改而进化。一般预测是，在修饰病毒中进化的变化将发生在已知与修饰基因相互作用的基因组部分中。该研究将通过实验数据对该框架进行直接测试。使用的病毒是无害的噬菌体 T7，它为其他病毒提供了一个良好的模型系统，因为人们对 T7 分子生物学已经了解很多，可以组装基因组网络，并且 T7 仅在少数细菌菌株上生长。这项工作将为公共卫生和分子流行病学以及基础生物学中的几个问题和目标提供有用的见解：（i）安全设计新基因组和制造重组疫苗的可行性； (ii) 我们如何能够很好地预测分子进化； (iii) 基因组相互作用在相关物种中是否保守； (iv) 如何检测工程基因组与自然基因组中进化的遗传特征。