Archaic human ancestry in East Asia

Edited by Richard G. Klein, Stanford University, Stanford, CA, and approved September 27, 2011 (received for review May 23, 2011)
October 31, 2011
108 (45) 18301-18306


Recent studies of ancient genomes have suggested that gene flow from archaic hominin groups to the ancestors of modern humans occurred on two separate occasions during the modern human expansion out of Africa. At the same time, decreasing levels of human genetic diversity have been found at increasing distance from Africa as a consequence of human expansion out of Africa. We analyzed the signal of archaic ancestry in modern human populations, and we investigated how serial founder models of human expansion affect the signal of archaic ancestry using simulations. For descendants of an archaic admixture event, we show that genetic drift coupled with ascertainment bias for common alleles can cause artificial but largely predictable differences in similarity to archaic genomes. In genotype data from non-Africans, this effect results in a biased genetic similarity to Neandertals with increasing distance from Africa. However, in addition to the previously reported gene flow between Neandertals and non-Africans as well as gene flow between an archaic human population from Siberia (“Denisovans”) and Oceanians, we found a significant affinity between East Asians, particularly Southeast Asians, and the Denisova genome—a pattern that is not expected under a model of solely Neandertal admixture in the ancestry of East Asians. These results suggest admixture between Denisovans or a Denisova-related population and the ancestors of East Asians, and that the history of anatomically modern and archaic humans might be more complex than previously proposed.

Continue Reading


We thank Noah Rosenberg, Michael Blum, Anders Götherström, Carina Schlebusch, Sohini Ramachandran, and two anonymous reviewers for valuable comments. Financial support was provided by the Swedish Research Council and the Lawski Foundation. Computations were performed on Swedish National Infrastructure for Computing (SNIC) and Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) resources (Project b2010050).

Supporting Information

Supporting Information (PDF)
Supporting Information


RL Cann, M Stoneking, AC Wilson, Mitochondrial DNA and human evolution. Nature 325, 31–36 (1987).
C Stringer, Modern human origins: Progress and prospects. Philos Trans R Soc Lond B Biol Sci 357, 563–579 (2002).
S Ramachandran, et al., Support from the relationship of genetic and geographic distance in human populations for a serial founder effect originating in Africa. Proc Natl Acad Sci USA 102, 15942–15947 (2005).
E Trinkaus, Early modern humans. Annu Rev Anthropol 34, 207–230 (2005).
P Mellars, Going east: New genetic and archaeological perspectives on the modern human colonization of Eurasia. Science 313, 796–800 (2006).
RG Klein, Out of Africa and the evolution of human behavior. Evol Anthropol 17, 267–281 (2008).
QD Atkinson, Phonemic diversity supports a serial founder effect model of language expansion from Africa. Science 332, 346–349 (2011).
M Stoneking, J Krause, Learning about human population history from ancient and modern genomes. Nat Rev Genet 12, 603–614 (2011).
M Nordborg, On the probability of Neanderthal ancestry. Am J Hum Genet 63, 1237–1240 (1998).
D Garrigan, Z Mobasher, T Severson, JA Wilder, MF Hammer, Evidence for archaic Asian ancestry on the human X chromosome. Mol Biol Evol 22, 189–192 (2005).
D Garrigan, MF Hammer, Reconstructing human origins in the genomic era. Nat Rev Genet 7, 669–680 (2006).
RE Green, et al., Analysis of one million base pairs of Neanderthal DNA. Nature 444, 330–336 (2006).
V Plagnol, JD Wall, Possible ancestral structure in human populations. PLoS Genet 2, e105 (2006).
JD Wall, KE Lohmueller, V Plagnol, Detecting ancient admixture and estimating demographic parameters in multiple human populations. Mol Biol Evol 26, 1823–1827 (2009).
M Krings, et al., Neandertal DNA sequences and the origin of modern humans. Cell 90, 19–30 (1997).
M Currat, L Excoffier, Modern humans did not admix with Neanderthals during their range expansion into Europe. PLoS Biol 2, e421 (2004).
D Serre, et al., No evidence of neandertal mtDNA contribution to early modern humans. Plos Biol 2, E57 (2004).
JP Noonan, et al., Sequencing and analysis of Neanderthal genomic DNA. Science 314, 1113–1118 (2006).
NJR Fagundes, et al., Statistical evaluation of alternative models of human evolution. Proc Natl Acad Sci USA 104, 17614–17619 (2007).
JD Wall, SK Kim, Inconsistencies in Neanderthal genomic DNA sequences. PLoS Genet 3, 1862–1866 (2007).
M DeGiorgio, M Jakobsson, NA Rosenberg, Out of Africa: Modern human origins special feature: Explaining worldwide patterns of human genetic variation using a coalescent-based serial founder model of migration outward from Africa. Proc Natl Acad Sci USA 106, 16057–16062 (2009).
MGB Blum, M Jakobsson, Deep divergences of human gene trees and models of human origins. Mol Biol Evol 28, 889–898 (2011).
RE Green, et al., A draft sequence of the Neandertal genome. Science 328, 710–722 (2010).
D Reich, et al., Genetic history of an archaic hominin group from Denisova Cave in Siberia. Nature 468, 1053–1060 (2010).
JA Hodgson, CM Bergey, TR Disotell, Neandertal genome: The ins and outs of African genetic diversity. Curr Biol 20, R517–R519 (2010).
MH Wolpoff, J Hawks, DW Frayer, K Hunley, Modern human ancestry at the peripheries: A test of the replacement theory. Science 291, 293–297 (2001).
DA Etler, The fossil evidence for human evolution in Asia. Annu Rev Anthropol 25, 275–301 (1996).
X Wu, On the origin of modern humans in China. Quatern Int 117, 131–140 (2004).
H Shang, H Tong, S Zhang, F Chen, E Trinkaus, An early modern human from Tianyuan Cave, Zhoukoudian, China. Proc Natl Acad Sci USA 104, 6573–6578 (2007).
W Liu, et al., Human remains from Zhirendong, South China, and modern human emergence in East Asia. Proc Natl Acad Sci USA 107, 19201–19206 (2010).
C Duarte, et al., The early Upper Paleolithic human skeleton from the Abrigo do Lagar Velho (Portugal) and modern human emergence in Iberia. Proc Natl Acad Sci USA 96, 7604–7609 (1999).
E Trinkaus, et al., An early modern human from the Peştera cu Oase, Romania. Proc Natl Acad Sci USA 100, 11231–11236 (2003).
E Trinkaus, European early modern humans and the fate of the Neandertals. Proc Natl Acad Sci USA 104, 7367–7372 (2007).
M Jakobsson, et al., Genotype, haplotype and copy-number variation in worldwide human populations. Nature 451, 998–1003 (2008).
JZ Li, et al., Worldwide human relationships inferred from genome-wide patterns of variation. Science 319, 1100–1104 (2008).
HM Cann, et al., A human genome diversity cell line panel. Science 296, 261–262 (2002).
J Novembre, S Ramachandran, Perspectives on human population structure at the cusp of the sequencing era. Annu Rev Genomics Hum Genet 12, 245–274 (2011).
MK Kuhner, P Beerli, J Yamato, J Felsenstein, Usefulness of single nucleotide polymorphism data for estimating population parameters. Genetics 156, 439–447 (2000).
A Albrechtsen, FC Nielsen, R Nielsen, Ascertainment biases in SNP chips affect measures of population divergence. Mol Biol Evol 27, 2534–2547 (2010).
A Keinan, JC Mullikin, N Patterson, D Reich, Measurement of the human allele frequency spectrum demonstrates greater genetic drift in East Asians than in Europeans. Nat Genet 39, 1251–1255 (2007).
DM Altshuler, et al., Integrating common and rare genetic variation in diverse human populations. Nature 467, 52–58 (2010).
I Surakka, et al., Founder population-specific HapMap panel increases power in GWA studies through improved imputation accuracy and CNV tagging. Genome Res 20, 1344–1351 (2010).
; Chimpanzee Sequencing and Analysis Consortium, Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437, 69–87 (2005).
N Patterson, AL Price, D Reich, Population structure and eigenanalysis. PLoS Genet 2, e190 (2006).
C Wang, et al., Comparing spatial maps of human population-genetic variation using Procrustes analysis. Stat Appl Genet Mol Biol 9, 13 (2010).
J Novembre, et al., Genes mirror geography within Europe. Nature 456, 98–101 (2008).
D Reich, K Thangaraj, N Patterson, AL Price, L Singh, Reconstructing Indian population history. Nature 461, 489–494 (2009).
EY Durand, N Patterson, D Reich, M Slatkin, Testing for ancient admixture between closely related populations. Mol Biol Evol 28, 2239–2252 (2011).
RM Durbin, et al., A map of human genome variation from population-scale sequencing. Nature 467, 1061–1073 (2010).
J Wang, et al., The diploid genome sequence of an Asian individual. Nature 456, 60–65 (2008).
S-M Ahn, et al., The first Korean genome sequence and analysis: Full genome sequencing for a socio-ethnic group. Genome Res 19, 1622–1629 (2009).
S Levy, et al., The diploid genome sequence of an individual human. PLoS Biol 5, e254 (2007).
NA Rosenberg, et al., Clines, clusters, and the effect of study design on the inference of human population structure. PLoS Genet 1, e70 (2005).
KL Hunley, ME Healy, JC Long, The global pattern of gene identity variation reveals a history of long-range migrations, bottlenecks, and local mate exchange: Implications for biological race. Am J Phys Anthropol 139, 35–46 (2009).
LJ Handley, A Manica, J Goudet, F Balloux, Going the distance: Human population genetics in a clinal world. Trends Genet 23, 432–439 (2007).
JS Friedlaender, et al., The genetic structure of Pacific Islanders. PLoS Genet 4, e19 (2008).
A Wollstein, et al., Demographic history of Oceania inferred from genome-wide data. Curr Biol 20, 1983–1992 (2010).
RN Gutenkunst, RD Hernandez, SH Williamson, CD Bustamante, Inferring the joint demographic history of multiple populations from multidimensional SNP frequency data. PLoS Genet 5, e1000695 (2009).
S Gravel, et al., Demographic history and rare allele sharing among human populations. Proc Natl Acad Sci USA 108, 11983–11988 (2011).
TD Dillehay Monte Verde: A Late Pleistocene Settlement in Chile (Smithsonian Institution Press, Washington, DC, 1997).
MTP Gilbert, et al., DNA from pre-Clovis human coprolites in Oregon, North America. Science 320, 786–789 (2008).
RM Harding, G McVean, A structured ancestral population for the evolution of modern humans. Curr Opin Genet Dev 14, 667–674 (2004).
P Gunz, et al., Early modern human diversity suggests subdivided population structure and a complex out-of-Africa scenario. Proc Natl Acad Sci USA 106, 6094–6098 (2009).
J Krause, et al., The complete mitochondrial DNA genome of an unknown hominin from southern Siberia. Nature 464, 894–897 (2010).
P Dixon, VEGAN, a package of R functions for community ecology. J Veg Sci 14, 927–930 (2003).
RR Hudson, Generating samples under a Wright-Fisher neutral model of genetic variation. Bioinformatics 18, 337–338 (2002).

Information & Authors


Published in

Go to Proceedings of the National Academy of Sciences
Go to Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences
Vol. 108 | No. 45
November 8, 2011
PubMed: 22042846


Submission history

Published online: October 31, 2011
Published in issue: November 8, 2011


  1. human origins
  2. ancient DNA


We thank Noah Rosenberg, Michael Blum, Anders Götherström, Carina Schlebusch, Sohini Ramachandran, and two anonymous reviewers for valuable comments. Financial support was provided by the Swedish Research Council and the Lawski Foundation. Computations were performed on Swedish National Infrastructure for Computing (SNIC) and Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) resources (Project b2010050).


This article is a PNAS Direct Submission.



Pontus Skoglund1 [email protected]
Department of Evolutionary Biology and
Mattias Jakobsson1 [email protected]
Department of Evolutionary Biology and
Science for Life Laboratory, Uppsala University, 75236 Uppsala, Sweden


To whom correspondence may be addressed. E-mail: [email protected] or [email protected].
Author contributions: P.S. and M.J. designed research; P.S. and M.J. performed research; P.S. analyzed data; and P.S. and M.J. wrote the paper.

Competing Interests

The authors declare no conflict of interest.

Metrics & Citations


Note: The article usage is presented with a three- to four-day delay and will update daily once available. Due to ths delay, usage data will not appear immediately following publication. Citation information is sourced from Crossref Cited-by service.

Citation statements



If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download.

Cited by


    View Options

    View options

    PDF format

    Download this article as a PDF file


    Get Access

    Login options

    Check if you have access through your login credentials or your institution to get full access on this article.

    Personal login Institutional Login

    Recommend to a librarian

    Recommend PNAS to a Librarian

    Purchase options

    Purchase this article to get full access to it.

    Single Article Purchase

    Archaic human ancestry in East Asia
    Proceedings of the National Academy of Sciences
    • Vol. 108
    • No. 45
    • pp. 18187-18566







    Share article link

    Share on social media