Experimental models of viral genome evolution

描述(申请人提供)：这项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，修改后的病毒将被适应，以观察它如何随着修改而进化。一般的预测是，在修改的病毒中进化的变化将发生在基因组中已知的与修改的基因相互作用的部分。这项研究将为这一框架提供直接的实验数据。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分子生物学有了很多了解，可以组装基因组网络，而且T7只在几个细菌菌株上生长。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)设计新基因组和安全地创造重组疫苗的可行性；(Ii)我们可以多好地预测分子进化；(Iii)基因组相互作用是否在相关物种中被保守；(Iv)如何在工程基因组和自然基因组中检测进化的遗传特征。

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.