Lundbeck Foundation GeoGenetics Centre, Globe Institute, University of Copenhagen, Copenhagen, Denmark.
GeoGenetics Group, Department of Zoology, University of Cambridge, Cambridge, UK.
Nature. 2024 Jan;625(7994):312-320. doi: 10.1038/s41586-023-06705-1. Epub 2024 Jan 10.
The Holocene (beginning around 12,000 years ago) encompassed some of the most significant changes in human evolution, with far-reaching consequences for the dietary, physical and mental health of present-day populations. Using a dataset of more than 1,600 imputed ancient genomes, we modelled the selection landscape during the transition from hunting and gathering, to farming and pastoralism across West Eurasia. We identify key selection signals related to metabolism, including that selection at the FADS cluster began earlier than previously reported and that selection near the LCT locus predates the emergence of the lactase persistence allele by thousands of years. We also find strong selection in the HLA region, possibly due to increased exposure to pathogens during the Bronze Age. Using ancient individuals to infer local ancestry tracts in over 400,000 samples from the UK Biobank, we identify widespread differences in the distribution of Mesolithic, Neolithic and Bronze Age ancestries across Eurasia. By calculating ancestry-specific polygenic risk scores, we show that height differences between Northern and Southern Europe are associated with differential Steppe ancestry, rather than selection, and that risk alleles for mood-related phenotypes are enriched for Neolithic farmer ancestry, whereas risk alleles for diabetes and Alzheimer's disease are enriched for Western hunter-gatherer ancestry. Our results indicate that ancient selection and migration were large contributors to the distribution of phenotypic diversity in present-day Europeans.
全新世(始于约 12000 年前)涵盖了人类进化中一些最重要的变化,对当今人口的饮食、身心健康产生了深远的影响。我们使用了一个包含 1600 多个推断出的古代基因组的数据集,模拟了从狩猎采集到农业和畜牧业在整个欧洲西部的过渡过程中的选择景观。我们确定了与新陈代谢相关的关键选择信号,包括 FADS 簇的选择比之前报道的更早,以及 LCT 基因座附近的选择比乳糖耐受等位基因的出现早几千年。我们还在 HLA 区域发现了强烈的选择,这可能是由于青铜时代病原体暴露的增加。我们利用古代个体来推断英国生物库中超过 40 万个样本的局部祖先轨迹,发现了欧洲各地新石器时代、青铜时代和中石器时代祖先的广泛分布差异。通过计算特定祖先的多基因风险评分,我们表明北欧和南欧之间的身高差异与草原祖先的差异有关,而不是选择,与情绪相关表型的风险等位基因在新石器时代农民的祖先中富集,而糖尿病和阿尔茨海默病的风险等位基因在西部狩猎采集者的祖先中富集。我们的研究结果表明,古代的选择和迁移是当今欧洲人表型多样性分布的主要贡献因素。