Park Su-Chan, Krug Joachim
Institut für Theoretische Physik, Universität zu Köln, Zülpicher Strasse 77, 50937 Köln, Germany.
Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):18135-40. doi: 10.1073/pnas.0705778104. Epub 2007 Nov 5.
Clonal interference, the competition between lineages arising from different beneficial mutations in an asexually reproducing population, is an important factor determining the tempo and mode of microbial adaptation. The standard theory of this phenomenon neglects the occurrence of multiple mutations as well as the correlation between loss by genetic drift and clonal competition, which is questionable in large populations. Working within the Wright-Fisher model with multiplicative fitness (no epistasis), we determine the rate of adaptation asymptotically for very large population sizes and show that the standard theory fails in this regime. Our study also explains the success of the standard theory in predicting the rate of adaptation for moderately large populations. Furthermore, we show that the nature of the substitution process changes qualitatively when multiple mutations are allowed for, because several mutations can be fixed in a single fixation event. As a consequence, the index of dispersion for counts of the fixation process displays a minimum as a function of population size, whereas the origination process of fixed mutations becomes completely regular for very large populations. We find that the number of mutations fixed in a single event is geometrically distributed as in the neutral case. These conclusions are based on extensive simulations combined with analytic results for the limit of infinite population size.
克隆干扰是指在无性繁殖群体中，由不同有益突变产生的谱系之间的竞争，是决定微生物适应速度和模式的一个重要因素。关于这一现象的标准理论忽略了多重突变的发生以及遗传漂变导致的损失与克隆竞争之间的相关性，而这在大群体中是值得怀疑的。在具有乘法适应性（无上位性）的赖特 - 费希尔模型中，我们针对非常大的群体规模渐近地确定了适应速率，并表明标准理论在这种情况下失效。我们的研究还解释了标准理论在预测中等规模群体适应速率方面的成功之处。此外，我们表明，当允许存在多重突变时，替代过程的性质会发生质的变化，因为几个突变可以在单个固定事件中被固定下来。因此，固定过程计数的离散指数作为群体规模的函数呈现出最小值，而对于非常大的群体，固定突变的起源过程变得完全规则。我们发现，在单个事件中固定的突变数量呈几何分布，就如同在中性情况下一样。这些结论基于广泛的模拟以及针对无限群体规模极限的分析结果。
