Zhang Wei, Sehgal Vasudha, Dinh Duy M, Azevedo Ricardo B R, Cooper Tim F, Azencott Robert
Department of Mathematics, University of Houston, Houston, TX 77204-3008, USA.
Theor Popul Biol. 2012 Mar;81(2):168-78. doi: 10.1016/j.tpb.2011.11.005. Epub 2011 Dec 3.
The rate and effect of available beneficial mutations are key parameters in determining how a population adapts to a new environment. However, these parameters are poorly known, in large part because of the difficulty of designing and interpreting experiments to examine the rare and intrinsically stochastic process of mutation occurrence. We present a new approach to estimate the rate and selective advantage of beneficial mutations that underlie the adaptation of asexual populations. We base our approach on the analysis of experiments that track the effect of newly arising beneficial mutations on the dynamics of a neutral marker in evolving bacterial populations and develop efficient estimators of mutation rate and selective advantage. Using extensive simulations, we evaluate the accuracy of our estimators and conclude that they are quite robust to the use of relatively low experimental replication. To validate the predictions of our model, we compare theoretical and experimentally determined estimates of the selective advantage of the first beneficial mutation to fix in a series of ten replicate populations. We find that our theoretical predictions are not significantly different from experimentally determined selection coefficients. Application of our method to suitably designed experiments will allow estimation of how population evolvability depends on demographic and initial fitness parameters.
可用有益突变的速率和效应是决定种群如何适应新环境的关键参数。然而,这些参数目前了解甚少,很大程度上是因为设计和解释实验来研究罕见且本质上具有随机性的突变发生过程存在困难。我们提出了一种新方法来估计无性种群适应过程中潜在有益突变的速率和选择优势。我们的方法基于对实验的分析,这些实验追踪新出现的有益突变对进化细菌种群中中性标记动态的影响,并开发了突变率和选择优势的有效估计器。通过广泛的模拟,我们评估了估计器的准确性,并得出结论,它们对于使用相对较低的实验重复次数相当稳健。为了验证我们模型的预测,我们比较了理论和实验确定的在一系列十个重复种群中固定的第一个有益突变的选择优势估计值。我们发现我们的理论预测与实验确定的选择系数没有显著差异。将我们的方法应用于适当设计的实验将能够估计种群进化能力如何依赖于种群统计学和初始适应度参数。