递归搭便车的鲁棒正演模拟
Robust forward simulations of recurrent hitchhiking
摘要：
进化的力量塑造了种群内的遗传多样性〈动〉性<动>，并促成了表型变异。特别是，经常性的积极选择吸引了显着的兴趣，在理论和实证研究。然而，大多数现有的理论模型，经常性的积极选择不能很容易地纳入现实的干扰效应，如干扰之间的选择网站，任意选择方案，和复杂的人口过程。可以通过执行正向群体遗传模拟来量化任意复杂的进化模型的影响，但是对于大的群体大小（$> 10^5$），正向模拟在计算上是禁止的。克服这些计算限制的一种常见方法是重新调整计算成本最高的参数，特别是人口规模。在这里，我们表明，特设的方法，经常性搭便车模型下的参数重新缩放并不总是提供足够准确的动态，潜在的扭曲模式的多样性模拟DNA序列。我们推导出一个扩展的经常性搭便车模型，这是适当的强选择在小的人口规模，并使用它来开发一种方法，参数重新调整，提供了最好的计算性能为给定的误差容限。我们进行了详细的理论分析的鲁棒性的参数空间的重新缩放。最后，我们将我们的重新缩放算法的参数，以前推断果蝇，并讨论实际的考虑，如选定的网站之间的干扰。
英文摘要：
Evolutionary forces shape patterns of genetic diversity within populations and contribute to phenotypic variation. In particular, recurrent positive selection has attracted significant interest in both theoretical and empirical studies. However, most existing theoretical models of recurrent positive selection cannot easily incorporate realistic confounding effects such as interference between selected sites, arbitrary selection schemes, and complicated demographic processes. It is possible to quantify the effects of arbitrarily complex evolutionary models by performing forward population genetic simulations, but forward simulations can be computationally prohibitive for large population sizes ($> 10^5$). A common approach for overcoming these computational limitations is rescaling of the most computationally expensive parameters, especially population size. Here, we show that ad hoc approaches to parameter rescaling under the recurrent hitchhiking model do not always provide sufficiently accurate dynamics, potentially skewing patterns of diversity in simulated DNA sequences. We derive an extension of the recurrent hitchhiking model that is appropriate for strong selection in small population sizes, and use it to develop a method for parameter rescaling that provides the best possible computational performance for a given error tolerance. We perform a detailed theoretical analysis of the robustness of rescaling across the parameter space. Finally, we apply our rescaling algorithms to parameters that were previously inferred for Drosophila, and discuss practical considerations such as interference between selected sites.
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