Archaic Human Ancestry in East Asia
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Archaic human ancestry in East Asia Pontus Skoglunda,1 and Mattias Jakobssona,b,1 aDepartment of Evolutionary Biology and bScience for Life Laboratory, Uppsala University, 75236 Uppsala, Sweden Edited by Richard G. Klein, Stanford University, Stanford, CA, and approved September 27, 2011 (received for review May 23, 2011) Recent studies of ancient genomes have suggested that gene flow adequate sampling of ancient and/or contemporary human ge- from archaic hominin groups to the ancestors of modern humans netic variation (23–25). occurred on two separate occasions during the modern human Although genome sequence data only exist for a small number expansion out of Africa. At the same time, decreasing levels of of individuals representing a handful of populations (8), genome- human genetic diversity have been found at increasing distance from wide SNP genotype data (34, 35) have been collected for a large Africa as a consequence of human expansion out of Africa. We number of populations from around the world, including urban, analyzed the signal of archaic ancestry in modern human popula- rural, and indigenous groups (36, 37). However, inference using tions, and we investigated how serial founder models of human genotype data is complicated by ascertainment bias; the bias that expansion affect the signal of archaic ancestry using simulations. For arises from discovering SNPs in sequence data from a limited descendants of an archaic admixture event, we show that genetic number of individuals resulting in enrichment of common alleles, drift coupled with ascertainment bias for common alleles can cause particularly in the populations from which the discovery panel was constructed (38, 39). To determine fine-scale patterns of artificial but largely predictable differences in similarity to archaic archaic admixture in the large collection of populations that have genomes. In genotype data from non-Africans, this effect results in been SNP genotyped, we need to understand the impact of as- a biased genetic similarity to Neandertals with increasing distance certainment bias on signals of archaic admixture. from Africa. However, in addition to the previously reported gene In this study, we analyzed patterns of genetic variation in fl fl ow between Neandertals and non-Africans as well as gene ow modern humans in the light of the two archaic genomes using “ ” between an archaic human population from Siberia ( Denisovans ) genotype data from a diverse set of extant populations, and we and Oceanians, we found a significant affinity between East Asians, found a signal of Denisova admixture in contemporary East Asian particularly Southeast Asians, and the Denisova genome—a pattern populations. We also studied the effect of ascertainment bias that is not expected under a model of solely Neandertal admixture under serial founder models of human expansion to show that the in the ancestry of East Asians. These results suggest admixture signal of Denisova admixture in contemporary East Asians is between Denisovans or a Denisova-related population and the opposite to the expectation under a model of solely Neandertal ancestors of East Asians, and that the history of anatomically admixture with the ancestral population of non-Africans followed modern and archaic humans might be more complex than previ- by greater genetic drift in East Asia than in Europe (40). ously proposed. Results human origins | ancient DNA To investigate the distribution of the signal of archaic human ancestry in a diverse and worldwide set of populations, we idespread evidence from genetics, linguistics, fossils, and extracted the Neandertal variant and the Denisova variant from Warcheology suggests that a wave of migration of anatomically the Neandertal (23) and Denisova (24) genomes at 40,656 loci modern humans out from Africa occurred within the last ∼100,000 overlapping with genotypes from 1,568 globally distributed ex- – tant humans (34, 35, 41, 42) and the chimpanzee genome (43) years (1 8). Until recently, evidence from genetic data has been fi inconclusive (9) with regard to the possibility of gene flow from the using largely the same lters for base quality, mapping quality, archaic human populations that already resided in Eurasia at the and postmortem degradation as previous studies (24). From each time of the out of Africa migration into the expanding population extant individual, we used one randomly sampled allele at each of anatomically modern humans, with some studies favoring some SNP to mimic the data from the archaic individuals, and we in- degree of admixture or shared ancestry (10–14) and others con- cluded one SNP from each pair of SNPs in high linkage dis- r2 > cluding either that admixture is unsupported or unnecessary to equilibrium ( 0.2), resulting in 38,848 SNPs. explain the data at hand (15–22). Principal Component Analysis of Archaic Ancestry. We performed Recent analyses of large-scale ancient genomic sequence data fi fi provided the most rigorously tested genetic evidence for ad- principal component analysis (PCA) (44) by de ning the rst two mixture so far, suggesting that a fraction of the ancestry of all principal components (PCs) using the Denisova, the Neandertal, modern humans of recent non-African ancestry traces back to and the chimpanzee and projected extant humans on the resulting Neandertals (23) and that a related archaic group, Denisovans, axes of variation (24). This setup resulted in PC1 describing gen- contributed an additional fraction of the ancestry of humans eral genetic similarity to archaic humans (represented by both the living in Oceania today (24). However, neither fine-scale geo- Neandertal and Denisova genomes) and PC2 contrasting genetic graphic patterns of archaic ancestry nor the impact of many similarity between Neandertal and Denisova. Under the assump- demographic events—such as founder events causing genetic tion of a common shared history between Neandertal and Deni- — sova (24) as well as no admixture between archaic populations and drift on archaic ancestry signals have been extensively studied. fi In addition, a model positing Neandertal-related gene flow into the ancestors of extant human populations since the diversi cation the ancestors of non-Africans—potentially occurring in the Middle East (23)—is supported by the possible Late Pleistocene ANTHROPOLOGY overlap of Neandertals and early modern humans in the Eastern Author contributions: P.S. and M.J. designed research; P.S. and M.J. performed research; Mediterranean (4, 6, 25). Similarly, the suggestion of archaic P.S. analyzed data; and P.S. and M.J. wrote the paper. Asian ancestry in Oceania is partly supported by some mor- The authors declare no conflict of interest. phological interpretations of the fossil record (4, 26). However, This article is a PNAS Direct Submission. similar, and arguably more suggestive (4, 6), morphological evi- Freely available online through the PNAS open access option. dence for admixture with archaic populations has been found in 1To whom correspondence may be addressed. E-mail: [email protected] or early modern human remains from East Asia (4, 6, 27–30) and [email protected]. EVOLUTION Europe (4, 31–33). Thus, it is possible that additional genomic This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10. signs of archaic admixture remain undetected because of in- 1073/pnas.1108181108/-/DCSupplemental. www.pnas.org/cgi/doi/10.1073/pnas.1108181108 PNAS | November 8, 2011 | vol. 108 | no. 45 | 18301–18306 Downloaded by guest on September 30, 2021 of modern humans (Fig. 1A), extant individuals are expected to be (Fig. 1C). Because it is well-known that PCs of modern human homogeneously distributed between archaic human and chim- genetic variation capture geography to some extent (35, 46), we panzee variations (24) (SI Materials and Methods). also computed PCs using modern human genetic variation in We recovered the previously reported (24) pattern—that ex- Eurasia (SI Results) and found that the top two PCs of differ- tant human variation is largely organized in three clusters cor- entiation between Europe and East Asia were correlated with −5 responding to Africans, Oceanians, and other non-Africans, the archaic ancestry signal (PC1: rs = 0.138, P < 10 ; PC2: rs = respectively (Fig. 1B and Fig. S1). In the worldwide collection of 0.090, P = 0.002). This result suggests that, if separated along the extant populations, we used Procrustes superimposition (45) to major axes of differentiation between Europe and East Asia, compare PC1 and PC2 with geographic coordinates (longitude individuals on the eastern end of the spectrum tend to be more and latitude) for each population and found that sampling lo- similar to archaic human genomes. In contrast, after correction cation was mirrored, to some extent, by archaic ancestry (indi- for multiple tests, we found no correlations between the archaic − viduals: Procrustes correlation = 0.127, P << 10 6; population ancestry signal and intraregional PCs within Europe, and we did means: Procrustes correlation = 0.309, P < 0.01). This pattern not find patterns of variation in archaic ancestry within Africa was expected given a model with two episodes of archaic gene and America that could not be explained by more recent ad- flow involving non-Africans and Oceanians (Fig. 2B) (23, 24). mixture with non-African populations (SI Results and Table S2). However, PC1 and PC2 were also correlated with geography To disentangle the signal of Denisova admixture from the in a region comprising Eurasia and the Americas (individuals: signal of Neanderthal admixture, we investigated the distribution − Procrustes correlation = 0.104, P < 10 4; population means: of PC2, which separated Denisovans and Neandertals, and found Procrustes correlation = 0.335, P = 0.017), which seemed in- that proximity to Neandertal increases with distance from Africa compatible with previously suggested admixture scenarios pos- (individuals: rs = 0.078, P = 0.010). However, East Asians were tulating that archaic ancestry is homogeneous in people of an exception to this trend in that they were significantly closer to European, Asian, and Native American descent (23, 24).