Hunter-gatherer admixture facilitated natural selection in Neolithic European farmers

Abstract

2 Department of Genetics, Schoolmultiple of Medicine, University of Pennsylvania, 13 Ancient DNAPerelman has revealed episodes of admixture in human prehistory Philadelphia, PA, USA 14 during geographic expansions associated with cultural innovations. One important *Correspondence to: tom.davy@crick.ac.uk, pontus.skoglund@crick.ac.uk 15 example is the expansion of Neolithic agricultural groups out of the Near East into $ co-senior authors 16 Europe, and their consequent admixture with Mesolithic hunter-gatherers. Ancient 17 genomes from this period provide an opportunity to study the role of admixture in bstract 18 providing new genetic variation for selection to act upon, and also to identify genomic ncient DNA has revealed multiple episodes of admixture in human prehistory 19 regions that resisted hunter-gatherer introgression and may thus contribute to ring geographic expansions associated with cultural innovations. One important 20 agricultural adaptations. We used genome-wide DNA from 728 individuals spanning ample is the expansion of Neolithic agricultural groups out of the Near East into 21 Mesolithic and Neolithic Europe to infer ancestry deviations in the genomes of urope, and their consequent admixture with Mesolithic hunter-gatherers. Ancient 22 admixed individuals, and to test for natural selection after admixture using a new enomes from this period provide an opportunity to study the role of admixture in 23 method based on testing for deviations from a genome-wide null distribution. We find oviding new genetic variation for selection to act upon, and also to identify genomic 24 that the region around the pigmentation-associated gene SLC24A5 shows the gions that resisted hunter-gatherer introgression and may thus contribute to 25 greatest overrepresentation of Neolithic ancestry in the genome (|Z| = 3.45). In ricultural adaptations. We used genome-wide DNA from 728 individuals spanning 26 contrast, we find the greatest overrepresentation of Mesolithic local ancestry across esolithic and Neolithic Europe to infer ancestry deviations in the genomes of 27 the key immunity locus that is the Major Histocompatibility Complex (MHC; |Z| > 4) mixed individuals, and to test for natural selection after admixture using a new 28 which also shows allele frequency deviations indicative of a selective sweep ethod based on testing for deviations from a-29genome-wide null distribution. We find 29 following admixture (p =1×10 ). This could reflect negative frequency dependent at the region around the pigmentation-associated gene SLC24A5 shows the 30 selection on MHC alleles common in Neolithic populations, or that Mesolithic alleles eatest overrepresentation of Neolithic ancestry in the genome (|Z| = 3.45). In 31 were positively selected for and facilitated adaptation by Neolithic populations to ntrast, we find the greatest overrepresentation of Mesolithic local ancestry across 32 pathogens, new diets, or other environmental factors. Our results extend previous e key immunity locus that is the Major Histocompatibility Complex (MHC; |Z| > 4) 33 results that highlight immune function and pigmentation as targets of adaptation in hich also shows allele frequency deviations indicative of a selective sweep 34 more recent populations to selection processes in the Stone Age, and demonstrate lowing admixture (p =1×10-29). This could reflect negative frequency dependent 35 that admixture facilitated selection by contributing new genetic variation. lection on MHC alleles common in Neolithic populations, or that Mesolithic alleles 36 ere positively selected for and facilitated adaptation by Neolithic populations to 37