The Selection Landscape and Genetic Legacy of Ancient Eurasians

作者：Evan K. Irving-Pease, Alba Refoyo-Martínez, Andrés Ingason, Alice Pearson, Anders Fischer, William Barrie, Karl-Göran Sjögren, Alma Halgren, Ruairidh Macleod, Fabrice Demeter, Rasmus Amund Henriksen, Tharsika Vimala, Hugh McColl, Andrew H. Vaughn, Aaron J. Stern, Leo Speidel, Gabriele Scorrano, Abigail Ramsøe, Andrew J. Schork, Anders Rosengren, Lei Zhao, Kristian Kristiansen, Peter H. Sudmant, Daniel J. Lawson, Richard Durbin, Thorfinn Sand Korneliussen, Thomas Werge, Morten E. Allentoft, Martin Sikora, Rasmus Nielsen, Fernando Racimo, Eske Willerslev · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2022 · DOI：10.1101/2022.09.22.509027 · 被引用次数：53 · 研究领域：Digestive system and related health、Genetic Associations and Epidemiology、Race, Genetics, and Society

Summary The Eurasian Holocene (beginning c. 12 thousand 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 an imputed dataset of >1600 complete ancient genome sequences, and new computational methods for locating selection in time and space, we reconstructed the selection landscape of the transition from hunting and gathering, to farming and pastoralism across West Eurasia. We identify major selection signals related to metabolism, possibly associated with the dietary shift occurring in this period. We show that the selection on loci such as the FADS cluster, associated with fatty acid metabolism, and the lactase persistence locus, began earlier than previously thought. A substantial amount of selection is also found in the HLA region and other loci associated with immunity, possibly due to the increased exposure to pathogens during the Neolithic, which may explain the current high prevalence of auto-immune disease, such as psoriasis, due to genetic trade-offs. By using ancient populations to infer local ancestry tracks in hundreds of thousands of samples from the UK Biobank, we find strong genetic differentiation among ancient Europeans in loci associated with anthropometric traits and susceptibility to several diseases that contribute to present-day disease burden. These were previously thought to be caused by local selection, but in f...