Clonal interference in large populations
Clonal interference in large populations
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DOI：
10.1073/pnas.0705778104
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发表时间：
2007-11-13
影响因子：
11.1
通讯作者：
Krug, Joachim
中科院分区：
文献类型：
--
作者：
Park, Su-Chan;Krug, Joachim
克隆干扰是无性繁殖种群中不同有益突变引起的谱系之间的竞争，是决定微生物适应克里思和模式的重要因素。这种现象的标准理论忽略了多个突变的发生，以及遗传漂变和克隆竞争之间的相关性，这在大种群中是值得怀疑的。工作范围内的赖特-费舍尔模型与乘法健身（无上位性），我们确定的适应率渐近非常大的人口规模，并表明，标准的理论失败，在这个政权。我们的研究还解释了标准理论在预测中等规模人口的适应率方面的成功。此外，我们表明，当允许多个突变时，取代过程的性质发生了质的变化，因为几个突变可以在一个固定事件中固定。因此，固定过程的计数的分散指数显示作为群体大小的函数的最小值，而固定突变的起源过程对于非常大的群体变得完全规则。我们发现单个事件中固定的突变数量与中性情况一样呈几何分布。这些结论是基于广泛的模拟结合分析结果的限制无限人口规模。
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.