Mutation rates: estimating phase variation rates when fitness differences are present and their impact on population structure
Mutation rates: estimating phase variation rates when fitness differences are present and their impact on population structure
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DOI：
10.1099/mic.0.25807-0
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发表时间：
2003-02-01
期刊：
影响因子：
2.8
通讯作者：
Gravenor, MB
中科院分区：
文献类型：
--
作者：
Saunders, NJ;Moxon, ER;Gravenor, MB
相位变化是被细菌病原体广泛利用的开-关转换机制。目前还没有标准化的相位变化率是如何确定实验，和突变率估计的传统方法可能不适合这个过程。在这里，突变率估计的历史回顾，描述现有的方法。本文还提出了一个新的数学模型，可应用于这一问题。该模型特别包括回复突变的混杂因素和替代表型之间的适应度差异的影响。这些是相位变化的中心特征，但很少被解决，结果是一些先前估计的相位变化率可能被显著高估。它表明，相反，该模型也可以用来调查健身差异，如果突变率是近似已知的。此外，通过对模型的随机模拟，探讨了头奖文化对突变率估计的影响。使用该模型，现实率和选择对人口结构的影响进行了研究。在不存在适合度差异的情况下，预计表型将在多代中保持稳定。因此，群体内表型变化的速率很可能主要由选择决定。如果在连续的时间点监测种群，可以更深入地了解突变率过程的种群动态。
Phase variation is a mechanism of ON-OFF switching that is widely utilized by bacterial pathogens. There is currently no standardization to how the rate of phase variation is determined experimentally, and traditional methods of mutation rate estimation may not be appropriate to this process. Here, the history of mutation rate estimation is reviewed, describing the existing methods available. A new mathematical model that can be applied to this problem is also presented. This model specifically includes the confounding factors of back-mutation and the influence of fitness differences between the alternate phenotypes. These are central features of phase variation but are rarely addressed, with the result that some previously estimated phase variation rates may have been significantly overestimated. It is shown that, conversely, the model can also be used to investigate fitness differences if mutation rates are approximately known. In addition, stochastic simulations of the model are used to explore the impact of jackpot cultures' on the mutation rate estimation. Using the model, the impact of realistic rates and selection on population structure is investigated. In the absence of fitness differences it is predicted that there will be phenotypic stability over many generations. The rate of phenotypic change within a population is likely, therefore, to be principally determined by selection. A greater insight into the population dynamics of mutation rate processes can be gained if populations are monitored over successive time points.