Institut für Populationsgenetik, Vetmeduni Vienna, Austria.
Vienna Graduate school of Population Genetics, Vetmeduni Vienna, Austria.
Genome Biol Evol. 2020 Mar 1;12(3):151-159. doi: 10.1093/gbe/evaa036.
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.
进化和重测序 (E&R) 研究调查了实验进化过程中适应性的基因组反应。由于重复种群在相同的受控环境中进化，因此经常使用对选择的一致反应来识别可靠的候选区域，这些区域是适应新环境的基础。然而，最近的研究表明，选择特征可能仅局限于一个或几个重复种群。这些选择特征通常具有较弱的统计支持，并且考虑到功能验证的困难，在将其视为功能分析的候选者之前，需要额外的证据。在这里，我们引入了一种实验程序来验证具有弱选择特征或仅在重复种群中出现的候选基因座。将主要 E&R 实验中进化的种群与原始祖先种群进行杂交，会降低已经达到高频率的候选等位基因的频率。我们假设，如果它们暴露在相同的环境中（二次 E&R 实验），那么真正的选择目标在与祖先创始人混合后会经历可重复的频率增加。使用这种方法，我们成功地验证了两个重叠的选择目标，它们在适应新温度范围的 Drosophila simulans 主要 E&R 实验中表现出相互排斥的选择特征。我们得出结论，除非上位性相互作用占主导地位，否则二次 E&R 实验可以可靠地确认在主要 E&R 实验中未被复制或仅显示低统计显著性的选择特征。这种实验对于为耗时的功能后续研究确定候选基因座的优先级特别有帮助。
