Erratum for Aidley et al., "Nonselective Bottlenecks Control the Divergence and Diversification of Phase-Variable Bacterial Populations".
Erratum for Aidley et al., "Nonselective Bottlenecks Control the Divergence and Diversification of Phase-Variable Bacterial Populations".
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DOI：
10.1128/mbio.00878-17
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发表时间：
2017-08-08
期刊：
影响因子：
6.4
通讯作者：
Bayliss CD
中科院分区：
文献类型：
--
作者：
Aidley J;Rajopadhye S;Akinyemi NM;Lango-Scholey L;Jones MA;Bayliss CD
许多致病菌和共生菌都存在相变异，并且是遗传变异的主要产生者。相位变化的一个假定的优点是对抗传输期间非选择性瓶颈所施加的可变性的减少。空肠弯曲菌是一种广泛存在的食源性致病菌，其基因组中含有多个相位可变位点，其快速、随机的变异是由超突变的简单重复序列区产生的。这些基因座可以占据大量的组合表达状态（相型），使人口迅速获得表型多样性。非选择性瓶颈的施加可以扰乱相型的相对频率，改变种群内的多样性和与初始种群的分歧。利用C.jejunipopulations的vitrotesting和一个简单的随机模拟相型变化，我们观察到，单细胞瓶颈产生低多样性的输出群体，但具有高或低分歧的双峰模式。相反，大的瓶颈只允许通过多样性的积累来分化，而在中间瓶颈中观察到这些极端之间的插值。这些模式对初始种群的遗传多样性敏感，但在一定的突变率和基因座数量范围内是稳定的。实验andin silicomodeling的定性相似性表明，所观察到的模式是强大的，适用于其他系统的本地化超突变是一个定义功能。我们的结论是，虽然相位变化将保持细菌种群的多样性，在面对中间的瓶颈，狭窄的传输相关的瓶颈可能会产生主机到主机的细菌表型的变化，因此随机变化的殖民化和疾病outcomes.IMPORTANCETransmission和宿主内传播的病原体与选择性和非选择性的瓶颈，显着降低人口的多样性。在几种细菌病原体中，已经进化出超变机制，介导特定表型（如表面结构）的高频可逆转换，从而抵消了与种群多样性减少相关的生物多样性减少。在这里，我们研究了超变简单序列重复序列的组合如何与非选择性瓶颈相互作用，通过使用随机计算机模型和实验数据forCampylobacter jejuni，一种食源性病原体。我们发现，瓶颈的大小从质量上改变了输出人口，大的瓶颈保持人口多样性，而小的瓶颈产生显着的变化，在特定的变体的流行。我们的结论是，狭窄的瓶颈能够在重复控制的细菌表型中产生宿主到宿主的变异，导致C. jejuni和其他具有类似超变机制的生物体在疾病结果中的随机人与人之间的变异。
Phase variation occurs in many pathogenic and commensal bacteria and is a major generator of genetic variability. A putative advantage of phase variation is to counter reductions in variability imposed by nonselective bottlenecks during transmission. Genomes ofCampylobacter jejuni, a widespread food-borne pathogen, contain multiple phase-variable loci whose rapid, stochastic variation is generated by hypermutable simple sequence repeat tracts. These loci can occupy a vast number of combinatorial expression states (phasotypes) enabling populations to rapidly access phenotypic diversity. The imposition of nonselective bottlenecks can perturb the relative frequencies of phasotypes, changing both within-population diversity and divergence from the initial population. Using bothin vitrotesting ofC. jejunipopulations and a simple stochastic simulation of phasotype change, we observed that single-cell bottlenecks produce output populations of low diversity but with bimodal patterns of either high or low divergence. Conversely, large bottlenecks allow divergence only by accumulation of diversity, while interpolation between these extremes is observed in intermediary bottlenecks. These patterns are sensitive to the genetic diversity of initial populations but stable over a range of mutation rates and number of loci. The qualitative similarities of experimental andin silicomodeling indicate that the observed patterns are robust and applicable to other systems where localized hypermutation is a defining feature. We conclude that while phase variation will maintain bacterial population diversity in the face of intermediate bottlenecks, narrow transmission-associated bottlenecks could produce host-to-host variation in bacterial phenotypes and hence stochastic variation in colonization and disease outcomes.IMPORTANCETransmission and within-host spread of pathogenic organisms are associated with selective and nonselective bottlenecks that significantly reduced population diversity. In several bacterial pathogens, hypermutable mechanisms have evolved that mediate high-frequency reversible switching of specific phenotypes, such as surface structures, and hence counteract bottleneck-associated reductions in population diversity. Here, we investigated how combinations of hypermutable simple sequence repeats interact with nonselective bottlenecks by using a stochastic computer model and experimental data forCampylobacter jejuni, a food-borne pathogen. We find that bottleneck size qualitatively alters the output populations, with large bottlenecks maintaining population diversity while small bottlenecks produce dramatic shifts in the prevalence of particular variants. We conclude that narrow bottlenecks are capable of producing host-to-host variation in repeat-controlled bacterial phenotypes, leading to a potential for stochastic person-to-person variations in disease outcome forC. jejuniand other organisms with similar hypermutable mechanisms.