Data from: Determining epistatic selection in admixed populations

When two diverging species begin hybridizing, selection against hybridization is likely driven not by single substitutions, but by interactions between incompatible mutations. To identify these incompatibilities in natural populations, researchers examine the extent of non-random associations between ancestry at physically unlinked loci in admixed populations. In this approach, which we call “AD scans”, locus-pairs with significantly positive “ancestry disequilibrium” (AD, i.e. locus-pairs that positively covary by ancestry) represent incompatible alleles. Past research has uniformly revealed an excess of locus-pairs with significantly positive AD, suggesting that dozens to hundreds of incompatibilities separate species. With forward simulations, we show that many realistic demographic scenarios, including recent and/or ongoing contact, generate a bias towards positive ancestry disequilibrium. We suggest steps that researchers can take to avoid pitfalls in interpreting AD scans, and present a novel measure of AD, which minimizes but does not fully eliminate bias in the AD distribution. We also show, by simulation, that the tail of the AD distribution is enriched for true incompatibilities. To illustrate the potential power and appropriate caution in interpretation of AD scans, we reanalyze previously published data from two admixed populations of Xiphophorus fishes. Our results imply that the prevalence of positive LD in admixed populations does not in itself support the idea that two-locus incompatibilities are widespread, but the co-enrichment of top AD hits across the two Xiphophorus populations supports the idea that AD scans can identify candidate interspecific incompatibilities.

当两个分化物种开始杂交时，针对杂交的选择不太可能由单个替换驱动，而是由不相容突变之间的互作所介导。为了在自然种群中鉴定此类不相容性，研究者会检测混合种群中物理上不连锁位点的祖先谱系间的非随机关联程度。这种被我们命名为"AD扫描（AD scans）"的分析策略中，呈现显著正"祖先不平衡（ancestry disequilibrium, AD）"的位点对（即随祖先谱系发生正向共变的位点对），即代表不相容等位基因。过往研究均一致观察到大量显著正祖先不平衡的位点对，这表明物种间存在数十乃至上百个不相容性位点。通过正向模拟（forward simulations），我们证实诸多符合实际的种群历史情景——包括近期且/或持续的种群接触——均会产生偏向正祖先不平衡的统计偏差。我们提出了研究者可用于规避AD扫描解读陷阱的操作步骤，并介绍了一种全新的AD度量方法，该方法可最小化但无法完全消除AD分布中的偏差。我们还通过模拟实验证明，AD分布的尾部区域会富集真实的不相容性位点。为了阐明AD扫描的潜在效力以及解读时需采取的审慎态度，我们重新分析了两项已发表的剑尾鱼属（Xiphophorus）混合种群数据。我们的研究结果表明，混合种群中正连锁不平衡（linkage disequilibrium, LD）的普遍存在本身并不能支持两位点不相容性广泛存在的观点，但两个剑尾鱼属混合种群中排名靠前的AD显著位点对存在共富集现象，这支持了AD扫描可用于鉴定种间不相容性候选位点的观点。