BACKGROUND The cline of human genetic diversity observable across Europe is recapitulated at a micro-geographic scale by variation within the Italian population. Besides resulting from extensive gene flow, this might be ascribable also to local adaptations to diverse ecological contexts evolved by people who anciently spread along the Italian Peninsula. Dissecting the evolutionary history of the ancestors of present-day Italians may thus improve the understanding of demographic and biological processes that contributed to shape the gene pool of European populations. However, previous SNP array-based studies failed to investigate the full spectrum of Italian variation, generally neglecting low-frequency genetic variants and examining a limited set of small effect size alleles, which may represent important determinants of population structure and complex adaptive traits. To overcome these issues, we analyzed 38 high-coverage whole-genome sequences representative of population clusters at the opposite ends of the cline of Italian variation, along with a large panel of modern and ancient Euro-Mediterranean genomes. RESULTS We provided evidence for the early divergence of Italian groups dating back to the Late Glacial and for Neolithic and distinct Bronze Age migrations having further differentiated their gene pools. We inferred adaptive evolution at insulin-related loci in people from Italian regions with a temperate climate, while possible adaptations to pathogens and ultraviolet radiation were observed in Mediterranean Italians. Some of these adaptive events may also have secondarily modulated population disease or longevity predisposition. CONCLUSIONS We disentangled the contribution of multiple migratory and adaptive events in shaping the heterogeneous Italian genomic background, which exemplify population dynamics and gene-environment interactions that played significant roles also in the formation of the Continental and Southern European genomic landscapes.

中文翻译：

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意大利人口的基因组历史概括了欧洲大陆和南欧人的关键进化动态。


背景技术欧洲各地可观察到的人类遗传多样性谱系通过意大利人口内部的变异在微观地理尺度上得到了概括。除了广泛的基因流动造成的之外，这也可能归因于古代沿着意大利半岛传播的人们对不同生态环境的适应。因此，剖析当今意大利人祖先的进化史可能会增进对人口和生物过程的理解，这些过程有助于塑造欧洲人口的基因库。然而，之前基于 SNP 阵列的研究未能调查意大利变异的全谱，通常忽略低频遗传变异并检查一组有限的小效应大小等位基因，这些等位基因可能代表种群结构和复杂适应性特征的重要决定因素。为了克服这些问题，我们分析了代表意大利变异谱系两端种群集群的 38 个高覆盖率全基因组序列，以及大量现代和古代欧洲-地中海基因组。结果我们提供了证据，证明意大利群体的早期分化可以追溯到冰期晚期，以及新石器时代和独特的青铜时代的迁徙进一步分化了他们的基因库。我们推断出来自气候温和的意大利地区的人们胰岛素相关位点的适应性进化，同时在地中海意大利人中观察到了对病原体和紫外线辐射的可能适应。其中一些适应性事件也可能具有二次调节的群体疾病或长寿倾向。 结论我们理清了多个迁徙和适应事件在塑造异质意大利基因组背景中的贡献，这例证了种群动态和基因-环境相互作用，它们在大陆和南欧基因组景观的形成中也发挥了重要作用。