Experimental models of viral genome evolution

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，病毒基因组将以简单的方式进行修改，修改后的病毒将适应观察它如何响应修改而进化。一般的预测是，在修饰的病毒中进化的变化将发生在已知与修饰的基因相互作用的基因组部分。这项研究将提供一个直接测试这个框架的实验数据。使用的病毒是无害的噬菌体T7，它为其他病毒提供了一个很好的模型系统，因为人们已经对T7的分子生物学有了很多了解，可以组装基因组网络，而且T7只能在少数几种细菌菌株上生长。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）工程新基因组和安全创建重组疫苗的可行性;（ii）我们可以如何预测分子进化;（iii）基因组相互作用是否在相关物种中保守;（iv）如何检测工程基因组与天然基因组中进化的遗传特征。

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.