Gordo Isabel, Gomes M Gabriela M, Reis Daniel G, Campos Paulo R A
Instituto Gulbenkian de Ciência, Oeiras, Portugal.
PLoS One. 2009;4(3):e4876. doi: 10.1371/journal.pone.0004876. Epub 2009 Mar 16.
We introduce a model for assessing the levels and patterns of genetic diversity in pathogen populations, whose epidemiology follows a susceptible-infected-recovered model (SIR). We model the population of pathogens as a metapopulation composed of subpopulations (infected hosts), where pathogens replicate and mutate. Hosts transmit pathogens to uninfected hosts. We show that the level of pathogen variation is well predicted by analytical expressions, such that pathogen neutral molecular variation is bounded by the level of infection and increases with the duration of infection. We then introduce selection in the model and study the invasion probability of a new pathogenic strain whose fitness (R(0)(1+s)) is higher than the fitness of the resident strain (R(0)). We show that this invasion probability is given by the relative increment in R(0) of the new pathogen (s). By analyzing the patterns of genetic diversity in this framework, we identify the molecular signatures during the replacement and compare these with those observed in sequences of influenza A.
我们引入了一个模型,用于评估病原体群体中的遗传多样性水平和模式,其流行病学遵循易感-感染-康复模型(SIR)。我们将病原体群体建模为由亚群体(受感染宿主)组成的集合种群,病原体在其中进行复制和突变。宿主将病原体传播给未感染的宿主。我们表明,病原体变异水平可以通过解析表达式得到很好的预测,即病原体中性分子变异受感染水平的限制,并随感染持续时间增加。然后,我们在模型中引入选择,并研究一种新致病菌株的入侵概率,该菌株的适应度(R(0)(1 + s))高于常驻菌株的适应度(R(0))。我们表明,这种入侵概率由新病原体的R(0)相对增量(s)给出。通过在这个框架中分析遗传多样性模式,我们识别出替换过程中的分子特征,并将这些特征与甲型流感序列中观察到的特征进行比较。