Several recent studies detected fine-scale genetic structure in human populations. Hence, groups conventionally treated as single populations harbour significant variation in terms of allele frequencies and patterns of haplotype sharing. It has been shown that these findings should be considered when performing studies of genetic associations and natural selection, especially when dealing with polygenic phenotypes. However, there is little understanding of the practical effects of such genetic structure on demography reconstructions and selection scans when focusing on recent population history. Here we tested the impact of population structure on such inferences using high-coverage (~30×) genome sequences of 2305 Estonians. We show that different regions of Estonia differ in both effective population size dynamics and signatures of natural selection. By analyzing identity-by-descent segments we also reveal that some Estonian regions exhibit evidence of a bottleneck 10–15 generations ago reflecting sequential episodes of wars, plague and famine, although this signal is virtually undetected when treating Estonia as a single population. Besides that, we provide a framework for relating effective population size estimated from genetic data to actual census size and validate it on the Estonian population. This approach may be widely used both to cross-check estimates based on historical sources as well as to get insight into times and/or regions with no other information available. Our results suggest that the history of human populations within the last few millennia can be highly region specific and cannot be properly studied without taking local genetic structure into account.

最近的几项研究发现了人类群体的精细遗传结构。因此，在等位基因频率和单倍型共享模式方面，传统上被视为单一群体的群体具有显着差异。已经表明，在进行遗传关联和自然选择的研究时，尤其是在处理多基因表型时，应考虑这些发现。但是，当关注最近的人口历史时，对这种遗传结构对人口结构重建和选择扫描的实际影响了解甚少。在这里，我们使用2305爱沙尼亚人的高覆盖率（〜30X）基因组序列测试了人口结构对此类推论的影响。我们表明，爱沙尼亚的不同地区在有效人口规模动态和自然选择的特征上都不同。通过分析按血统划分的人群，我们还发现，爱沙尼亚的一些地区在10至15代之前就显示出瓶颈现象，反映出战争，瘟疫和饥荒的连续发作，尽管在将爱沙尼亚作为一个单一人群对待时实际上并未发现。除此之外，我们提供了一个框架，可将根据遗传数据估算的有效人口规模与实际人口普查规模相关联，并在爱沙尼亚人口中进行验证。这种方法既可以广泛用于基于历史来源对估计进行交叉检查，又可以在没有其他可用信息的情况下深入了解时间和/或地区。