Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
J Theor Biol. 2011 May 7;276(1):150-8. doi: 10.1016/j.jtbi.2011.01.033. Epub 2011 Feb 1.
Pathogen species with high mutation rates are likely to accumulate deleterious mutations that reduce their reproductive potential within the host. By altering the within-host growth rate of the pathogen, the deleterious mutation load has the potential to affect epidemiological properties such as prevalence, mean pathogen load, and the mean duration of infections. Here, I examine an epidemiological model that allows for multiple segregating mutations that affect within-host replication efficiency. The model demonstrates a complex range of outcomes depending on pathogen mutation rate, including two distinct, widely separated mutation rates associated with high pathogen prevalence. The low mutation rate prevalence peak is associated with small amounts of genetic diversity within the pathogen population, relatively stable prevalence and infection dynamics, and genetic variation partitioned between hosts. The high mutation rate peak is characterized by considerable genetic diversity both within and between hosts, relatively frequent invasions by more virulent types, and is qualitatively similar to an RNA virus quasispecies. The two prevalence peaks are separated by a valley where natural selection favors evolution toward the optimal within-host state, which is associated with high virulence and relatively rapid host mortality. Both chronic and acute infections are examined using stochastic forward simulations.
高突变率的病原体物种很可能会积累有害突变，从而降低其在宿主中的繁殖潜力。通过改变病原体在体内的生长速度，有害突变负荷有可能影响流行率、平均病原体负荷和感染持续时间等流行病学特性。在这里，我研究了一个允许影响体内复制效率的多个分离突变的流行病学模型。该模型根据病原体突变率展示了一系列复杂的结果，包括与高病原体流行率相关的两个截然不同、广泛分离的突变率。低突变率流行峰值与病原体种群内的遗传多样性数量少、相对稳定的流行和感染动态以及宿主之间的遗传变异有关。高突变率峰值的特点是宿主内和宿主间的遗传多样性都相当大，更具毒性的类型更频繁地入侵，并且与 RNA 病毒准种定性相似。两个流行峰值之间是一个山谷，其中自然选择有利于向最佳体内状态进化，这与高毒力和相对较快的宿主死亡率有关。使用随机正向模拟检查了慢性和急性感染。
