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Genome-wide patterns of selection in 230 ancient Eurasians

Abstract

Ancient DNA makes it possible to observe natural selection directly by analysing samples from populations before, during and after adaptation events. Here we report a genome-wide scan for selection using ancient DNA, capitalizing on the largest ancient DNA data set yet assembled: 230 West Eurasians who lived between 6500 and 300 bc, including 163 with newly reported data. The new samples include, to our knowledge, the first genome-wide ancient DNA from Anatolian Neolithic farmers, whose genetic material we obtained by extracting from petrous bones, and who we show were members of the population that was the source of Europe’s first farmers. We also report a transect of the steppe region in Samara between 5600 and 300 bc, which allows us to identify admixture into the steppe from at least two external sources. We detect selection at loci associated with diet, pigmentation and immunity, and two independent episodes of selection on height.

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Figure 1: Population relationships of samples.
Figure 2: Genome-wide scan for selection.
Figure 3: Allele frequencies for five genome-wide significant signals of selection.
Figure 4: Polygenic selection on height.

Accession codes

Primary accessions

European Nucleotide Archive

Data deposits

The aligned sequences are available through the European Nucleotide Archive under accession number PRJEB11450. The Human Origins genotype datasets including ancient individuals can be found at (http://genetics.med.harvard.edu/reich/Reich_Lab/Datasets.html).

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Acknowledgements

We thank P. de Bakker, J. Burger, C. Economou, E. Fornander, Q. Fu, F. Hallgren, K. Kirsanow, A. Mittnik, I. Olalde, A. Powell, P. Skoglund, S. Tabrizi and A. Tandon for discussions, suggestions about SNPs to include, or contribution to sample preparation or data curation. We thank S. Pääbo, M. Meyer, Q. Fu and B. Nickel for collaboration in developing the 1240k capture reagent. We thank J. M. V. Encinas and M. E. Prada for allowing us to resample La Braña 1. I.M. was supported by the Human Frontier Science Program LT001095/2014-L. C.G. was supported by the Irish Research Council for Humanities and Social Sciences (IRCHSS). F.G. was supported by a grant of the Netherlands Organization for Scientific Research, no. 380-62-005. A.K., P.K. and O.M. were supported by RFBR no. 15-06-01916 and RFH no. 15-11-63008 and O.M. by a state grant of the Ministry of Education and Science of the Russia Federation no. 33.1195.2014/k. J.K. was supported by ERC starting grant APGREID and DFG grant KR 4015/1-1. K.W.A. was supported by DFG grant AL 287 / 14-1. C.L.-F. was supported by a BFU2015-64699-P grant from the Spanish government. W.H. and B.L. were supported by Australian Research Council DP130102158. R.P. was supported by ERC starting grant ADNABIOARC (263441), and an Irish Research Council ERC support grant. D.R. was supported by US National Science Foundation HOMINID grant BCS-1032255, US National Institutes of Health grant GM100233, and the Howard Hughes Medical Institute.

Author information

Authors and Affiliations

Authors

Contributions

W.H., R.P. and D.R. supervised the study. S.A.R., J.L.A., J.M.B., E.C., F.G., A.K., P.K., M.L., H.M., O.M., V.M., M.A.R., J.R., J.M.V., J.K., A.C., K.W.A., D.B., D.A., C.L., W.H., R.P. and D.R. assembled archaeological material. I.M., I.L., N.R., S.M., N.P., S.D., J.P., W.H. and D.R. analysed genetic data. N.R., E.H., K.St., D.F., M.N., K.Si., C.G., E.R.J., B.L., C.L. and W.H. performed wet laboratory ancient DNA work. I.M., I.L. and D.R. wrote the manuscript with input from all co-authors.

Corresponding authors

Correspondence to Iain Mathieson, Wolfgang Haak, Ron Pinhasi or David Reich.

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Competing interests

The authors declare no competing financial interests.

Extended data figures and tables

Extended Data Figure 1 Efficiency and cost-effectiveness of 1240k capture.

We plot the number of raw sequences against the mean coverage of analysed SNPs after removal of duplicates, comparing the 163 samples for which capture data are newly reported in this study, against the 102 samples analysed by shotgun sequencing in ref. 5. We caution that the true cost is more than that of sequencing alone.

Extended Data Figure 2 Early isolation and later admixture between farmers and steppe populations.

a, Mainland European populations later than 3000 bc are better modelled with steppe ancestry as a third ancestral population, (closer correspondence between empirical and estimated f4-statistics as estimated by resnorm; Methods). b, Later (post-Poltavka) steppe populations are better modelled with Anatolian Neolithic as a third ancestral population. c, Estimated mixture proportions of mainland European populations without steppe ancestry. d, Estimated mixture proportions of Eurasian steppe populations without Anatolian Neolithic ancestry. e, Estimated mixture proportions of later populations with both steppe and Anatolian Neolithic ancestry. f, Admixture plot at k = 17 showing population differences over time and space. EN, Early Neolithic; MN, Middle Neolithic; LN, Late Neolithic; BA, Bronze Age; LNBA, Late Neolithic and Bronze Age.

Extended Data Figure 3 Regional association plots.

Locuszoom60 plots for genome-wide significant signals. Points show the –log10 P value for each SNP, coloured according to their linkage disequilibrium (LD; units of r2) with the most associated SNP. The blue line shows the recombination rate, with scale on right hand axis in centimorgans per megabase (cM/Mb). Genes are shown in the lower panel of each subplot.

Extended Data Figure 4 PCA of selection populations and derived allele frequencies for genome-wide significant signals.

a, Ancient samples projected onto principal components of modern samples, as in Fig. 1, but labelled according to selection populations defined in Extended Data Table 1. b, Allele frequency plots as in Fig. 3. Six signals not included in Fig. 3—for SLC22A4 we show both rs272872, which is our strongest signal, and rs1050152, which was previously hypothesized to be under selection, and we also show SLC24A5, which is not genome-wide significant but is discussed in the main text.

Extended Data Figure 5 Motala haplotypes carrying the derived, selected EDAR allele.

This figure compares the genotypes at all sites within 150 kb of rs3827760 (in blue) for the 6 Motala samples and 20 randomly chosen CHB (Chinese from Beijing) and CEU (Utah residents with northern and western European ancestry) samples. Each row is a sample and each column is a SNP. Grey means homozygous for the major (in CEU) allele. Pink denotes heterozygous and red indicates homozygous for the other allele. For the Motala samples, an open circle means that there is only a single sequence, otherwise the circle is coloured according to the number of sequences observed. Three of the Motala samples are heterozygous for rs3827760 and the derived allele lies on the same haplotype background as in present-day East Asians. The only other ancient samples with evidence of the derived EDAR allele in this data set are two Afanasievo samples dating to 3300–3000 bc, and one Scythian dating to 400–200 bc (not shown).

Extended Data Figure 6 Estimated power of the selection scan.

a, Estimated power for different selection coefficients (s) for a SNP that is selected in all populations for either 50, 100 or 200 generations. b, Effect of increasing sample size, showing estimated power for a SNP selected for 100 generations, with different amounts of data, relative to the main text. c, Effect of admixture from Yoruba (YRI) into one of the modern populations, showing the effect on the genomic inflation factor (blue, left axis) and the power to detect selection on a SNP selected for 100 generations with a selection coefficient of 0.02. d, Effect of mis-specification of the mixture proportions. Here 0 on the x axis corresponds to the proportions we used, and 1 corresponds to a random mixture matrix.

Extended Data Table 1 230 ancient individuals analysed in this study
Extended Data Table 2 Key f-statistics used to support claims about population history
Extended Data Table 3 Twelve genome-wide significant signals of selection

Supplementary information

Supplementary Information

This file contains Supplementary Text comprising: Archaeological context for 83 newly reported ancient samples (Section 1) and Population interactions between Anatolia, mainland Europe, and the Eurasian steppe (Section 2) with additional references. (PDF 1045 kb)

Supplementary Data 1

This file contains information about 230 ancient samples used in this study. (XLSX 101 kb)

Supplementary Data 2

This file shows FST between ancient and modern populations. (XLSX 26 kb)

Supplementary Data 3

This file contains Genome-wide selection scan results and allele frequencies. (TXT 71292 kb)

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Mathieson, I., Lazaridis, I., Rohland, N. et al. Genome-wide patterns of selection in 230 ancient Eurasians. Nature 528, 499–503 (2015). https://doi.org/10.1038/nature16152

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