Beneficial mutations drive adaptive evolution, yet their selective advantage does not ensure their fixation. Haldane's application of single-type branching process theory showed that genetic drift alone could cause the extinction of newly arising beneficial mutations with high probability. With linkage, deleterious mutations will affect the dynamics of beneficial mutations and might further increase their extinction probability. Here, we model the lineage dynamics of a newly arising beneficial mutation as a multitype branching process. Our approach accounts for the combined effects of drift and the stochastic accumulation of linked deleterious mutations, which we call lineage contamination We first study the lineage-contamination phenomenon in isolation, deriving dynamics and survival probabilities (the complement of extinction probabilities) of beneficial lineages. We find that survival probability is zero when [Formula: see text] where U is deleterious mutation rate and [Formula: see text] is the selective advantage of the beneficial mutation in question, and is otherwise depressed below classical predictions by a factor bounded from below by [Formula: see text] We then put the lineage contamination phenomenon into the context of an evolving population by incorporating the effects of background selection. We find that, under the combined effects of lineage contamination and background selection, ensemble survival probability is never zero but is depressed below classical predictions by a factor bounded from below by [Formula: see text] where [Formula: see text] is mean selective advantage of beneficial mutations, and [Formula: see text] This factor, and other bounds derived from it, are independent of the fitness effects of deleterious mutations. At high enough mutation rates, lineage contamination can depress fixation probabilities to values that approach zero. This fact suggests that high mutation rates can, perhaps paradoxically, (1) alleviate competition among beneficial mutations, or (2) potentially even shut down the adaptive process. We derive critical mutation rates above which these two events become likely.

译文

:有益突变驱动适应性进化,但其选择性优势并不能确保其固定性。 Haldane在单一类型分支过程理论中的应用表明,仅遗传漂移就很有可能导致新出现的有益突变的灭绝。通过连锁,有害突变将影响有益突变的动力学,并可能进一步增加其灭绝的可能性。在这里,我们将新出现的有益突变的谱系动力学建模为多类型分支过程。我们的方法考虑了漂移和链接的有害突变的随机积累的综合影响,我们称其为谱系污染。我们首先单独研究谱系污染现象,得出有益谱系的动力学和生存概率(灭绝概率的补充)。我们发现,当[公式:参见文本]时,生存概率为零,其中U是有害突变率,而[公式:参见文本]是所讨论的有益突变的选择优势,而在经典预测之下,则受以下因素的限制:然后,通过结合背景选择的影响,将血统污染现象纳入不断发展的种群的背景中。我们发现,在谱系污染和背景选择的共同作用下,整体生存概率永远不会为零,但在经典预测之下却受到以下因素的压制:[公式:参见文本]其中[公式:参见文本]是平均选择性的有益突变的优势,以及[公式:参见文本]此因子以及由此衍生的其他范围与有害突变的适应性效果无关。在足够高的突变率下,谱系污染会使固定概率降低到接近零的值。这一事实表明,高突变率可能(可能反常的是)(1)减轻了有益突变之间的竞争,或者(2)甚至可能关闭适应性过程。我们得出临界突变率,高于这两个事件就有可能发生。

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