The selection landscape and genetic legacy of ancient Eurasians

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 se...

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Bibliographic Details
Published in:	Nature (London) 2024-01, Vol.625 (7994), p.312-320
Main Authors:	Irving-Pease, Evan K, Refoyo-Martínez, Alba, Barrie, William, Ingason, Andrés, Pearson, Alice, Fischer, Anders, Sjögren, Karl-Göran, Halgren, Alma S, Macleod, Ruairidh, Demeter, Fabrice, Henriksen, Rasmus A, Vimala, Tharsika, McColl, Hugh, Vaughn, Andrew H, Speidel, Leo, Stern, Aaron J, Scorrano, Gabriele, Ramsøe, 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
Format:	Article
Language:	eng
Subjects:	Affect Agriculture - history Alleles Alzheimer Disease - genetics Alzheimer's disease Archaeology Arkeologi Asia - ethnology Asian - genetics Biobanks Bronze Age Datasets Diabetes mellitus Diabetes Mellitus - genetics Europe - ethnology European People - genetics Evolution Farmers Farmers - history Genetic Loci - genetics Genetic Predisposition to Disease Genetics Genetik Genome, Human - genetics Genomes Haplotypes History, Ancient Holocene Human Migration Humans Hunter-gatherers Hunting Hunting - history Iron Age Lactase Mesolithic Multifactorial Inheritance - genetics Multigene Family - genetics Neolithic Neurodegenerative diseases Pastoralism Phenotype Phenotypes Risk Selection, Genetic Steppes Stone Age UK Biobank
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Summary:	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.
ISSN:	0028-0836 1476-4687 1476-4687