Hunter-gatherer admixture facilitated natural selection in Neolithic European farmers

Abstract

Ancient DNA has revealed multiple episodes of admixture in human prehistory during geographic expansions associated with cultural innovations. One important example is the expansion of Neolithic agricultural groups out of the Near East into Europe, and their consequent admixture with Mesolithic hunter-gatherers. Ancient genomes from this period provide an opportunity to study the role of admixture in providing new genetic variation for selection to act upon, and also to identify genomic regions that resisted hunter-gatherer introgression and may thus contribute to agricultural adaptations. We used genome-wide DNA from 728 individuals spanning Mesolithic and Neolithic Europe to infer ancestry deviations in the genomes of admixed individuals, and to test for natural selection after admixture using a new method based on testing for deviations from a genome-wide null distribution. We find that the region around the pigmentation-associated gene SLC24A5 shows the greatest overrepresentation of Neolithic ancestry in the genome (|Z| = 3.45). In contrast, we find the greatest overrepresentation of Mesolithic local ancestry across the key immunity locus that is the Major Histocompatibility Complex (MHC; |Z| > 4) which also shows allele frequency deviations indicative of a selective sweep following admixture (p =1x10-29). This could reflect negative frequency dependent selection on MHC alleles common in Neolithic populations, or that Mesolithic alleles were positively selected for and facilitated adaptation by Neolithic populations to pathogens, new diets, or other environmental factors. Our results extend previous results that highlight immune function and pigmentation as targets of adaptation in more recent populations to selection processes in the Stone Age, and demonstrate that admixture facilitated selection by contributing new genetic variation.

Social and genetic diversity among the first farmers of Central Europe

“…We detect evidence of long-term balancing selection in the HLA region on chromosome 6, with elevated B1 scores (Figure 6), consistent with previous evidence of balancing selection 18 at this locus in Neolithic Europeans 39 . A second notable finding is 29 genes with evidence of balancing selection in the ALPc and LBK (Supplementary Table 12).…”

Genetic adaptation to pathogens and increased risk of inflammatory disorders in post-Neolithic Europe

“…We next reasoned that the arrival of populations from the Pontic-Caspian region ∼4,500 ya may have brought beneficial variants that continued to be subject to positive selection in the resulting admixed population, a process known as adaptive admixture. 58 , 59 In this case, we would expect to see a positive correlation between Pontic Steppe ancestry and the probability of carrying positively selected alleles. However, no significant differences were observed between positively selected alleles and matched controls (p adj > 0.05 for all matched samples; STAR Methods ), and no systematic bias was observed in the ancestry of simulated and observed aDNA samples ( Figure S4 A).…”

Admixture as a source for HLA variation in Neolithic European farming communities

“…Interestingly, the major frequency changes (>20%) between EF and LF mainly affect HLA class II alleles (Table S3). A recent SNPbased study (29) has shown that the HLA region, especially the DQB1 locus (HLA class II), is enriched for WHG ancestry in Neolithic individuals as a result of adaptive admixture. This process has been shown to be relevant within the HLA context, potentially driving specific alleles towards higher frequencies (30,31).…”