Department of Biology, Duke University, Durham, North Carolina 27708.
Am Nat. 2013 Oct;182(4):494-513. doi: 10.1086/672000. Epub 2013 Aug 20.
The evolutionary rates of RNA viruses can differ from one another by several orders of magnitude. Much of this variation has been explained by differences in viral mutation rates and selective environments. However, substitution rates also vary considerably across viral populations belonging to the same species. In particular, viral lineages from epidemic regions tend to have higher substitution rates than those from endemic regions, and lineages from populations with higher contact rates tend to have higher substitution rates than those from populations with lower contact rates. We address the mechanism behind these patterns by using a nested modeling approach, whereby we integrate within-host viral replication dynamics with a population-level epidemiological model. Through numerical simulations and analytical approximations, we show that variation in viral substitution rates over the course of an infection, coupled with differences in age of infection of transmitting hosts under different epidemiological scenarios, can explain these evolutionary patterns. We further derive analytical estimates of expected substitution rate differences under epidemic versus endemic epidemiological conditions. By comparing these estimates to empirical data for four viral species, we show that these factors are sufficient to explain observed variation in substitution rates in three of four cases. This work shows that even in neutrally evolving viral populations, epidemiological dynamics can alter substitution rates via the interplay between within-host replication dynamics and population-level disease dynamics.
RNA 病毒的进化率可以相差几个数量级。这种差异在很大程度上可以通过病毒突变率和选择环境的差异来解释。然而，在同一物种的病毒群体中，替代率也会有很大的差异。特别是来自流行地区的病毒谱系比来自地方性地区的病毒谱系的替代率更高，来自接触率较高的人群的病毒谱系比来自接触率较低的人群的病毒谱系的替代率更高。我们通过使用嵌套建模方法来解决这些模式背后的机制，该方法将体内病毒复制动力学与群体水平的流行病学模型相结合。通过数值模拟和分析近似，我们表明在感染过程中病毒替代率的变化，加上在不同流行病学情况下传播宿主感染年龄的差异，可以解释这些进化模式。我们进一步推导出在流行和地方性流行病学条件下预期替代率差异的分析估计。通过将这些估计值与四种病毒的经验数据进行比较，我们表明在四种情况中的三种情况下，这些因素足以解释替代率的观察到的变化。这项工作表明，即使在中性进化的病毒群体中，流行病学动态也可以通过体内复制动态和群体水平疾病动态之间的相互作用来改变替代率。
