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. 2015 Dec 24;528(7583):499-503.
doi: 10.1038/nature16152. Epub 2015 Nov 23.

Genome-wide patterns of selection in 230 ancient Eurasians

Iain Mathieson  1 , Iosif Lazaridis  1   2 , Nadin Rohland  1   2 , Swapan Mallick  1   2   3 , Nick Patterson  2 , Songül Alpaslan Roodenberg  4 , Eadaoin Harney  1   3 , Kristin Stewardson  1   3 , Daniel Fernandes  5 , Mario Novak  5   6 , Kendra Sirak  5   7 , Cristina Gamba  5   8 , Eppie R Jones  8 , Bastien Llamas  9 , Stanislav Dryomov  10   11 , Joseph Pickrell  1 , Juan Luís Arsuaga  12   13 , José María Bermúdez de Castro  14 , Eudald Carbonell  15   16 , Fokke Gerritsen  17 , Aleksandr Khokhlov  18 , Pavel Kuznetsov  18 , Marina Lozano  15   16 , Harald Meller  19 , Oleg Mochalov  18 , Vyacheslav Moiseyev  20 , Manuel A Rojo Guerra  21 , Jacob Roodenberg  22 , Josep Maria Vergès  15   16 , Johannes Krause  23   24 , Alan Cooper  9 , Kurt W Alt  19   25   26 , Dorcas Brown  27 , David Anthony  27 , Carles Lalueza-Fox  28 , Wolfgang Haak  9   23 , Ron Pinhasi  5 , David Reich  1   2   3
Affiliations

Genome-wide patterns of selection in 230 ancient Eurasians

Iain Mathieson et al. Nature. .

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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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Extended Data Figure 1
Extended Data Figure 1. Efficiency and cost-effectiveness of 1240k capture
We plot the number of raw sequences against the mean coverage of analyzed SNPs after removal of duplicates, comparing the 163 samples for which capture data are reported in this study, against the 102 samples analyzed by shotgun sequencing in ref. We caution that the true cost is more than that of sequencing alone.
Extended Data Figure 2
Extended Data Figure 2. Early isolation and later admixture between farmers and steppe populations
A: Mainland European populations later than 3000 BCE are better modeled with steppe ancestry as a 3rd ancestral population. B: Later (post-Poltavka) steppe populations are better modeled with Anatolian Neolithic as a 3rd 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.
Extended Data Figure 3
Extended Data Figure 3. Regional association plots
Locuszoom plots for genome-wide significant signals. Points show the –log10 P-value for each SNP, colored according to their LD with the most associated SNP. The blue line shows the recombination rate, with scale on right hand axis. Genes are shown in the lower panel of each subplot.
Extended Data Figure 4
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 labeled 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
Extended Data Figure 5. Motala haplotypes carrying the derived, selected EDAR allele
This figure compares the genotypes at all sites within 150kb 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 homozygous for the other allele. For the Motala samples, an open circle means that there is only a single sequence otherwise the circle is colored 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 dataset are two Afanasievo samples dating to 3300-3000 BCE, and one Scythian dating to 400-200 BCE (not shown).
Extended Data Figure 6
Extended Data Figure 6. Estimated power of the selection scan
A: Estimated power for different selection coefficients 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.
Figure 1
Figure 1. Population relationships of samples
A. Locations color-coded by date, with a random jitter added for visibility (8 Afanasievo and Andronovo samples lie further east and are not shown). B: Principal component analysis of 777 modern West Eurasian samples (grey), with 221 ancient samples projected onto the first two principal component axes and labeled by culture. Abbreviations: [E/M/L]N Early/Middle/Late Neolithic, LBK Linearbandkeramik, [E/W]HG Eastern/Western hunter-gatherer, [E]BA [Early] Bronze Age, IA Iron Age.
Figure 2
Figure 2. Genome-wide scan for selection
GC-corrected −log10 p-value for each marker (Methods). The red dashed line represents a genome-wide significance level of 0.5×10−8. Genome-wide significant points filtered because there were fewer than two other genome-wide significant points within 1Mb are shown in grey. Inset: QQ plots for corrected −log10 P-values for different categories of potentially functional SNPs (Methods). Truncated at −log10(P-value)=30. All curves are significantly different from neutral expectation.
Figure 3
Figure 3. Allele frequencies for five genome-wide significant signals of selection
Dots and solid lines show maximum likelihood frequency estimates and a 1.9-log-likelihood support interval for the derived allele frequency in each ancient population. Horizontal dashed lines show allele frequencies in the four modern 1000 Genomes populations. Abbreviations for ancient populations; AEN: Anatolian Neolithic; HG: hunter-gatherer; CEM: Central European Early and Middle Neolithic; INC: Iberian Neolithic and Chalcolithic; CLB: Central European Late Neolithic and Bronze Age; STP: Steppe. The Hunter-Gatherer, Early Farmer and Steppe Ancestry classifications correspond approximately to the three populations used in the genome-wide scan with some differences (See Extended Data Table 1 for details).
Figure 4
Figure 4. Polygenic selection on height
A. Estimated genetic heights. Boxes show 0.05–0.95 posterior densities for population mean genetic height (Methods). Dots show the maximum likelihood point estimate. Arrows show major population relationships, dashed lines represent ancestral populations. V’s show potential independent selection events. B: Z scores for the pairwise polygenic selection test. Positive if the column population is taller than the row population. Abbreviations; AN: Anatolian Neolithic; HG: hunter-gatherer; CEM: Central European Early and Middle Neolithic; INC: Iberian Neolithic and Chalcolithic; CLB: Central European Late Neolithic and Bronze Age; STP: Steppe; CEU: Utah residents with northern and western European ancestry; IBS: Iberian population in Spain.
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