进化医学是现代进化理论在疾病健康领域的新应用。在传染病领域，结合这一新学科理论，明晰传染病病原体的传播与进化规律，是制定科学有效的传染病防控策略的必要前提。目前，该领域的计算方法、统计分析策略和进化模型还很缺乏，成为了进化医学在传染病领域进一步应用的瓶颈。本研究拟以乙脑病毒疫苗株为研究对象，探讨乙脑病毒在细胞内持续感染进程中的进化模型，并揭示中性和用药环境下的进化动力学。在方法学方面，我们拟建立基于单分子测序的RNA病毒种群突变检测方法，RNA病毒种群突变频率计算方法，以及各因素同多基因突变相关性的计算模型。在此基础上，构建病毒种群在细胞中的进化模型，包括突变率的估计模型，中性选择的微进化模型，以及耐药选择下的负选择模型，最终发现病毒种群在细胞持续感染过程中的微进化规律。本项目面向整个重大研究计划中“微进化机制的基本理论与法则”，预期建立病毒微进化研究所需要的生物信息学和计算生物学新方法。

Evolutionary medicine is a new application of modern evolutionary theory in the field of health problems. In the field of infectious diseases, discerning the spread and evolution of infectious disease pathogens is essential to develop the scientific and effective prevention and control strategies. At present, the lack of computational methods, statistical analysis methods and evolutionary models has become the bottleneck for applying evolutionary medicine in the field of infectious diseases. In this study, we are planning to use Japanese encephalitis virus (JEV) vaccine strain as a model virus to study evolutionary dynamics of JEV quasispecies during persistent infection and under selective pressures. We proposed to employ single molecule sequencing technology and second generation sequencing to access viral quasispecies population. The methods to estimate mutation rate, mutation frequency, the correlation between mutation and other factor under neutral and non-neutral evolution are to be established. The aim of project is to understand the basic theory and mechanism of viral quasispecies micro-evolution, and also to establish new bioinformatics and computational methodology for micro-evolution of RNA viruses.