Power of neutrality tests to detect bottlenecks and hitchhiking
Power of neutrality tests to detect bottlenecks and hitchhiking
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DOI：
10.1007/s00239-003-0027-y
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发表时间：
2003-01-01
影响因子：
3.9
通讯作者：
Veuille, M
中科院分区：
文献类型：
--
作者：
Depaulis, F;Mousset, S;Veuille, M
几个中立性测试拒绝一个简单的瓶颈模型的能力在一个联合框架中得到了检验。考虑了几个检验，包括一些依赖于突变频谱的检验，一些反映了数据的连锁不平衡结构。我们评估了年龄和瓶颈强度的影响，以及它们之间的相互作用。我们对比了两个性质不同的瓶颈效应，这取决于它们的强度。在系谱方面，在严重的瓶颈时期，所有的谱系结合在一起，产生了样本的明星般的基因系谱。在瓶颈之后的一段时间里，一旦出现新的突变，它们往往会显示出过多的稀有变异和略多的单倍型。相反，更温和的瓶颈允许几个谱系在人口崩溃中幸存下来，导致内部分支较长的平衡谱系。事件发生后不久，数据往往显示中频变异过多，单倍型不足。我们表明，对于适度的测序工作，只有在允许发生突变的中间时间段之后，才能检测到严重的瓶颈，最好是通过频谱统计。对于较新的事件，尤其是使用单倍型统计数据，可以更容易地检测到中等瓶颈。最后，对于单个轨迹，瓶颈结果与简单搭便车模型的结果非常接近。主要区别在于适度扰动后突变和单倍型的频率分布。搭便车增加了罕见的祖先突变的数量，并导致了更主要的单倍型类别。因此，尽管这两个过程之间有许多共同的特征，但搭便车不能严格地由瓶颈来建模。
The power of several neutrality tests to reject a simple bottleneck model is examined in a coalescent framework. Several tests are considered including some relying on the frequency spectrum of mutations and some reflecting the linkage disequilibrium structure of the data. We evaluate the effect of the age and of the strength of the bottleneck, and their interaction. We contrast two qualitatively different bottleneck effects depending on their strength. In genealogical terms, during severe bottlenecks, all lineages coalesce leading to a star-like gene genealogy of the sample. Some time after the bottleneck, once new mutations have arisen, they tend to show an excess of rare variants and a slight excess of haplotypes. On the contrary, more moderate bottlenecks allow several lineages to survive the demographic crash, leading to a balanced genealogy with long internal branches. Soon after the event, data tend to show an excess of intermediate frequency variants and a deficit of haplotypes. We show that for moderate sequencing efforts, severe bottlenecks can be detected only after an intermediate time period has allowed for mutations to occur, preferably by frequency spectrum statistics. Moderate bottlenecks can be more easily detected for more recent events, especially using haplotype statistics. Finally, for a single locus, the bottleneck results closely approximate those of a simple hitchhiking model. The main difference concerns the frequency distribution of mutations and haplotypes after moderate perturbations. Hitchhiking increases the number of rare ancestral mutations and leads to a more predominant major haplotype class. Thus, despite a number of common features between the two processes, hitchhiking cannot be strictly modeled by bottlenecks.