The selection landscape and genetic legacy of ancient Eurasians

• 成果类型: Article
• 署名作者: Irving-Pease, Evan K.; Refoyo-Martinez, Alba; Barrie, William; Ingason, Andres; Pearson, Alice; Fischer, Anders; Sjoegren, Karl-Goeran; Halgren, Alma S.; Macleod, Ruairidh; Demeter, Fabrice; Henriksen, Rasmus A.; Vimala, Tharsika; Mccoll, Hugh; Vaughn, Andrew H.; Speidel, Leo; Stern, Aaron J.; Scorrano, Gabriele; Ramsoe, Abigail; Schork, Andrew J.; Rosengren, Anders; Zhao, Lei; Kristiansen, Kristian; Iversen, Astrid K. N.; Fugger, Lars; Sudmant, Peter H.; Lawson, Daniel J.; Durbin, Richard; Korneliussen, Thorfinn; Werge, Thomas; Allentoft, Morten E.; Sikora, Martin; Nielsen, Rasmus; Racimo, Fernando; Willerslev, Eske
• 署名单位: University of Copenhagen; University of Cambridge; University of Copenhagen; Copenhagen University Hospital; University of Cambridge; University of Cambridge; University of Gothenburg; University of California System; University of California Berkeley; University of London; University College London; Centre National de la Recherche Scientifique (CNRS); Museum National d'Histoire Naturelle (MNHN); Universite Paris Cite; University of California System; University of California Berkeley; Francis Crick Institute; Translational Genomics Research Institute; University of Oxford; University of Oxford; Aarhus University; University of Oxford; University of Bristol; Wellcome Trust Sanger Institute; University of Copenhagen; University of Copenhagen; Copenhagen University Hospital; Curtin University; University of California System; University of California Berkeley; University of Bremen; University of Bremen
• 刊物名称: Nature
• ISSN/ISSBN: 0028-4211
• DOI: 10.1038/s41586-023-06705-1
• 发表日期: 2024-01-11
• 页码: 312-320
• 关键词: copy number variation; positive selection; alzheimers-disease; lactase-persistence; natural-selection; human-populations; uk biobank; adaptation; HISTORY; skin

摘要

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 genomes1, 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. Analyses of imputed ancient genomes and of samples from the UK Biobank indicate that ancient selection and migration were large contributors to the distribution of phenotypic diversity in present-day Europeans.