Secondary Evolve and Resequencing: An Experimental Confirmation of Putative Selection Targets without Phenotyping
Secondary Evolve and Resequencing: An Experimental Confirmation of Putative Selection Targets without Phenotyping
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DOI：
10.1093/gbe/evaa036
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发表时间：
2020-03-01
影响因子：
3.3
通讯作者：
Schloetterer, Christian
中科院分区：
文献类型：
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作者：
Burny, Claire;Nolte, Viola;Schloetterer, Christian
进化和重测序 (E&R) 研究调查实验进化过程中适应的基因组反应。由于重复群体在相同的受控环境中进化，因此对重复中选择的一致反应经常用于识别适应新环境的可靠候选区域。然而，最近的工作表明，选择签名可以仅限于一个或几个重复。这些选择签名通常具有较弱的统计支持，并且考虑到功能验证的困难，在将它们视为功能分析的候选者之前需要额外的证据。在这里，我们介绍了一个实验程序来验证具有弱或重复特异性选择签名的候选基因座。将来自初级 E&R 实验的进化群体与祖先创始人群体进行杂交会降低已达到高频率的候选等位基因的频率。我们假设，如果真正的选择目标暴露在相同的环境中，那么在与祖先创始人混合后，他们将经历可重复的频率增加（二次 E&R 实验）。使用这种方法，我们成功验证了两个重叠的选择目标，这在模拟果蝇适应新温度条件的初级 E&R 实验中显示出相互排斥的选择特征。我们得出的结论是，二次 E&R 实验提供了对选择特征的可靠确认，除非上位相互作用占主导地位，否则这些选择特征要么不会被复制，要么在初级 E&R 实验中仅显示出较低的统计显着性。此类实验特别有助于确定候选基因座的优先顺序，以进行耗时的功能后续研究。
Evolve and resequencing (E&R) studies investigate the genomic responses of adaptation during experimental evolution. Because replicate populations evolve in the same controlled environment, consistent responses to selection across replicates are frequently used to identify reliable candidate regions that underlie adaptation to a new environment. However, recent work demonstrated that selection signatures can be restricted to one or a few replicate(s) only. These selection signatures frequently have weak statistical support, and given the difficulties of functional validation, additional evidence is needed before considering them as candidates for functional analysis. Here, we introduce an experimental procedure to validate candidate loci with weak or replicate-specific selection signature(s). Crossing an evolved population from a primary E&R experiment to the ancestral founder population reduces the frequency of candidate alleles that have reached a high frequency. We hypothesize that genuine selection targets will experience a repeatable frequency increase after the mixing with the ancestral founders if they are exposed to the same environment (secondary E&R experiment). Using this approach, we successfully validate two overlapping selection targets, which showed a mutually exclusive selection signature in a primary E&R experiment of Drosophila simulans adapting to a novel temperature regime. We conclude that secondary E&R experiments provide a reliable confirmation of selection signatures that either are not replicated or show only a low statistical significance in a primary E&R experiment unless epistatic interactions predominate. Such experiments are particularly helpful to prioritize candidate loci for time-consuming functional follow-up investigations.