Most human populations exhibit an excess of high‐frequency variants, leading to a U‐shaped site‐frequency spectrum (uSFS). This pattern has been generally interpreted as a signature of ongoing episodes of positive selection, or as evidence for a mis‐assignment of ancestral/derived allelic states, but uSFS has also been observed in populations receiving gene flow from a ghost population, in structured populations, or after range expansions. In order to better explain the prevalence of high‐frequency variants in humans and other populations, we describe here which patterns of gene flow and population demography can lead to uSFS by using extensive coalescent simulations. We find that uSFS can often be observed in a population if gene flow brings a few ancestral alleles from a well‐differentiated population. Gene flow can either consist in single pulses of admixture or continuous immigration, but different demographic conditions are necessary to observe uSFS in these two scenarios. Indeed, an extremely low and recent gene flow is required in the case of single admixture events, while with continuous immigration, uSFS occurs only if gene flow started recently at a high rate or if it lasted for a long time at a low rate. Overall, we find that a neutral uSFS occurs under more restrictive conditions in populations having received single pulses of gene flow than in populations exposed to continuous gene flow. We also show that the uSFS observed in human populations from the 1000 Genomes Project can easily be explained by gene flow from surrounding populations without requiring past episodes of positive selection. These results imply that uSFS should be common in non‐isolated populations, such as most wild or domesticated plants and animals.

中文翻译：

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基因流是导致高频等位基因过量的简单原因

大多数人口都表现出过多的高频变异，从而导致了U形站点频谱（uSFS）。通常将这种模式解释为正在进行正选择的情节的特征，或作为祖先/衍生的等位基因状态的错误分配的证据，但在从虚构群体接受基因流的人群，结构性人群中也观察到了uSFS。 ，或范围扩展后。为了更好地解释人类和其他人群中高频变异的流行，我们在此描述通过使用广泛的合并模拟，哪些基因流和人口统计学的模式可以导致uSFS。我们发现，如果基因流从高度分化的人群中带来一些祖先等位基因，则通常可以在人群中观察到uSFS。基因流既可以是单一脉冲混合，也可以是连续迁移，但是在这两种情况下观察uSFS都需要不同的人口统计学条件。确实，在单一混合物事件中，需要极低的近期基因流量，而对于连续迁移，只有当基因流量最近以高速率开始或长时间以低速率持续时，uSFS才会发生。总的来说，我们发现中性uSFS在受到单一基因流脉冲的人群中比在暴露于连续基因流的人群中更受限制。我们还表明，从1000个基因组计划的人群中观察到的uSFS可以轻松地由周围人群的基因流来解释，而无需过去的积极选择。