Studies of human population history have the goal of finding out what happened in our past, in terms of population origins, migrations, relationships, admixture and changes in population size — that is, the demographic history of populations. Genome-wide data sets are now transforming this field.
The study of fossil DNA, or ancient DNA, has been revolutionized by technological developments in high-throughput sequencing. Three ancient hominin nuclear genome sequences have now been published: from a Neanderthal; from a recently discovered extinct hominin group from Siberia, Denisovans; and from a native Greenlander (Saqqaq).
Many new genome sequences from modern humans have been obtained by the 1000 Genomes Project, as well as by several other human genome and exome sequencing efforts.
Genome-wide SNP data are becoming increasingly available from many populations of anthropological interest.
Increases in computational power have enabled more sophisticated use of genome-scale data. There have been two important advances for human population studies: unsupervised analyses and model-based analyses.
Issues that can be addressed using genome-wide data include the African origin of modern humans and the number of dispersals.
Genome-wide data, both from SNP arrays and from complete genome sequencing, are becoming increasingly abundant and are now even available from extinct hominins. These data are providing new insights into population history; in particular, when combined with model-based analytical approaches, genome-wide data allow direct testing of hypotheses about population history. For example, genome-wide data from both contemporary populations and extinct hominins strongly support a single dispersal of modern humans from Africa, followed by two archaic admixture events: one with Neanderthals somewhere outside Africa and a second with Denisovans that (so far) has only been detected in New Guinea. These new developments promise to reveal new stories about human population history, without having to resort to storytelling.
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Green, R. E. et al. A draft sequence of the Neandertal genome. Science 328, 710–722 (2010). The first genome sequence from an extinct hominin, Neanderthals, demonstrating a signal of Neanderthal admixture in the genome of all studied non-African modern humans.
Rasmussen, M. et al. Ancient human genome sequence of an extinct Palaeo-Eskimo. Nature 463, 757–762 (2010). The first genome sequence from an ancient human. This study demonstrates the feasibility of obtaining high-quality genome sequences from permafrost-preserved human hair and suggests the occurrence of a migration event that is not evident from contemporary human populations.
Reich, D. et al. Genetic history of an archaic hominin group from Denisova Cave in Siberia. Nature 468, 1053–1060 (2010). The second genome sequence from an extinct hominin, Denisovans, demonstrating that they were a sister group to Neanderthals and that they admixed with the ancestors of Melanesians.
Durbin, R. M. et al. A map of human genome variation from population-scale sequencing. Nature 467, 1061–1073 (2010).
Li, Y. et al. Resequencing of 200 human exomes identifies an excess of low-frequency non-synonymous coding variants. Nature Genet. 42, 969–972 (2010).
Schuster, S. C. et al. Complete Khoisan and Bantu genomes from southern Africa. Nature 463, 943–947 (2010).
Henn, B. M. et al. Hunter-gatherer genomic diversity suggests a southern African origin for modern humans. Proc. Natl Acad. Sci. USA 108, 5154–5162 (2011).
Jakobsson, M. et al. Genotype, haplotype and copy-number variation in worldwide human populations. Nature 451, 998–1003 (2008).
Li, J. Z. et al. Worldwide human relationships inferred from genome-wide patterns of variation. Science 319, 1100–1104 (2008).
Lopez Herraez, D. et al. Genetic variation and recent positive selection in worldwide human populations: evidence from nearly 1 million SNPs. PLoS ONE 4, e7888 (2009).
Reich, D., Thangaraj, K., Patterson, N., Price, A. L. & Singh, L. Reconstructing Indian population history. Nature 461, 489–494 (2009). In addition to using genome-wide SNP data to provide a detailed genetic history of India, this study introduced several important methods for analysing such data. These methods were used in subsequent studies to demonstrate an admixture signal in modern humans with Neanderthals and Denisovans.
Xing, J. et al. Toward a more uniform sampling of human genetic diversity: a survey of worldwide populations by high-density genotyping. Genomics 96, 199–210 (2010).
Wollstein, A. et al. Demographic history of Oceania inferred from genome-wide data. Curr. Biol. 20, 1983–1992 (2010). These authors used genome-wide SNP data and a novel approach for accounting for ascertainment bias to infer multiple dispersals of humans to Asia and Oceania, and to investigate the complicated admixture history of Remote Oceanian populations.
Jobling, M. A. & Tyler-Smith, C. The human Y chromosome: an evolutionary marker comes of age. Nature Rev. Genet. 4, 598–612 (2003).
Pakendorf, B. & Stoneking, M. Mitochondrial DNA and human evolution. Annu. Rev. Genomics Hum. Genet. 6, 165–183 (2005).
Miller, W. et al. Sequencing the nuclear genome of the extinct woolly mammoth. Nature 456, 387–390 (2008).
Lander, E. S. Initial impact of the sequencing of the human genome. Nature 470, 187–197 (2011).
Paabo, S. et al. Genetic analyses from ancient DNA. Annu. Rev. Genet. 38, 645–679 (2004).
Higuchi, R., Bowman, B., Freiberger, M., Ryder, O. A. & Wilson, A. C. DNA sequences from the quagga, an extinct member of the horse family. Nature 312, 282–284 (1984).
Paabo, S. Molecular cloning of Ancient Egyptian mummy DNA. Nature 314, 644–645 (1985).
Green, R. E. et al. The Neandertal genome and ancient DNA authenticity. EMBO J. 28, 2494–2502 (2009).
Green, R. E. et al. A complete Neandertal mitochondrial genome sequence determined by high-throughput sequencing. Cell 134, 416–426 (2008).
Poinar, H. N. et al. Metagenomics to paleogenomics: large-scale sequencing of mammoth DNA. Science 311, 392–394 (2006).
Cooper, A. & Poinar, H. N. Ancient DNA: do it right or not at all. Science 289, 1139 (2000).
Paabo, S. Ancient DNA: extraction, characterization, molecular cloning, and enzymatic amplification. Proc. Natl Acad. Sci. USA 86, 1939–1943 (1989).
Krause, J. et al. Multiplex amplification of the mammoth mitochondrial genome and the evolution of Elephantidae. Nature 439, 724–727 (2006).
Briggs, A. W. et al. Patterns of damage in genomic DNA sequences from a Neandertal. Proc. Natl Acad. Sci. USA 104, 14616–14621 (2007).
Maricic, T., Whitten, M. & Paabo, S. Multiplexed DNA sequence capture of mitochondrial genomes using PCR products. PLoS ONE 5, e14004 (2010).
Briggs, A. W. et al. Targeted retrieval and analysis of five Neandertal mtDNA genomes. Science 325, 318–321 (2009).
Krings, M. et al. Neandertal DNA sequences and the origin of modern humans. Cell 90, 19–30 (1997).
Krause, J. et al. A complete mtDNA genome of an early modern human from Kostenki, Russia. Curr. Biol. 20, 231–236 (2010).
Gilbert, M. T. et al. Paleo-Eskimo mtDNA genome reveals matrilineal discontinuity in Greenland. Science 320, 1787–1789 (2008).
Wall, J. D. & Kim, S. K. Inconsistencies in Neanderthal genomic DNA sequences. PLoS Genet. 3, 1862–1866 (2007).
Hofreiter, M., Jaenicke, V., Serre, D., Haeseler Av, A. & Paabo, S. DNA sequences from multiple amplifications reveal artifacts induced by cytosine deamination in ancient DNA. Nucleic Acids Res. 29, 4793–4799 (2001).
Brotherton, P. et al. Novel high-resolution characterization of ancient DNA reveals C > U-type base modification events as the sole cause of post mortem miscoding lesions. Nucleic Acids Res. 35, 5717–5728 (2007).
Briggs, A. W. et al. Removal of deaminated cytosines and detection of in vivo methylation in ancient DNA. Nucleic Acids Res. 38, e87 (2010).
Adler, C. J., Haak, W., Donlon, D. & Cooper, A. Survival and recovery of DNA from ancient teeth and bones. J. Arch. Sci. 38, 956–964 (2011).
Paten, B., Herrero, J., Beal, K., Fitzgerald, S. & Birney, E. Enredo and Pecan: genome-wide mammalian consistency-based multiple alignment with paralogs. Genome Res. 18, 1814–1828 (2008).
Nielsen, R. Population genetic analysis of ascertained SNP data. Hum. Genomics 1, 218–224 (2004).
Albrechtsen, A., Nielsen, F. C. & Nielsen, R. Ascertainment biases in SNP chips affect measures of population divergence. Mol. Biol. Evol. 27, 2534–2547 (2010).
Clark, A. G., Hubisz, M. J., Bustamante, C. D., Williamson, S. H. & Nielsen, R. Ascertainment bias in studies of human genome-wide polymorphism. Genome Res. 15, 1496–1502 (2005).
Lao, O. et al. Correlation between genetic and geographic structure in Europe. Curr. Biol. 18, 1241–1248 (2008).
Novembre, J. et al. Genes mirror geography within Europe. Nature 456, 98–101 (2008).
Hodges, E. et al. Genome-wide in situ exon capture for selective resequencing. Nature Genet. 39, 1522–1527 (2007).
Burbano, H. A. et al. Targeted investigation of the Neandertal genome by array-based sequence capture. Science 328, 723–725 (2010).
Krause, J. et al. The complete mitochondrial DNA genome of an unknown hominin from southern Siberia. Nature 464, 894–897 (2010).
Reich, D., Price, A. L. & Patterson, N. Principal component analysis of genetic data. Nature Genet. 40, 491–492 (2008).
Pritchard, J. K., Stephens, M. & Donnelly, P. Inference of population structure using multilocus genotype data. Genetics 155, 945–959 (2000). This paper introduced the widely used STRUCTURE program for inferring ancestry and admixture from multi-locus data at the individual level rather than the population level.
Tang, H., Peng, J., Wang, P. & Risch, N. J. Estimation of individual admixture: analytical and study design considerations. Genet. Epidemiol. 28, 289–301 (2005).
Beaumont, M. A. & Rannala, B. The Bayesian revolution in genetics. Nature Rev. Genet. 5, 251–261 (2004).
Hey, J. & Machado, C. A. The study of structured populations — new hope for a difficult and divided science. Nature Rev. Genet. 4, 535–543 (2003).
Kuhner, M. K. Coalescent genealogy samplers: windows into population history. Trends Ecol. Evol. 24, 86–93 (2009).
Hey, J. Isolation with migration models for more than two populations. Mol. Biol. Evol. 27, 905–920 (2010).
Hey, J. & Nielsen, R. Integration within the Felsenstein equation for improved Markov chain Monte Carlo methods in population genetics. Proc. Natl Acad. Sci. USA 104, 2785–2790 (2007).
Bertorelle, G. & Excoffier, L. Inferring admixture proportions from molecular data. Mol. Biol. Evol. 15, 1298–1311 (1998).
Bryc, K. et al. Genome-wide patterns of population structure and admixture in West Africans and African Americans. Proc. Natl Acad. Sci. USA 107, 786–791 (2010).
Hellenthal, G., Auton, A. & Falush, D. Inferring human colonization history using a copying model. PLoS Genet. 4, e1000078 (2008).
Moorjani, P. et al. The history of African gene flow into Southern Europeans, Levantines, and Jews. PLoS Genet. 7, e1001373 (2011).
Price, A. L. et al. Sensitive detection of chromosomal segments of distinct ancestry in admixed populations. PLoS Genet. 5, e1000519 (2009).
Pugach, I., Matveyev, R., Wollstein, A., Kayser, M. & Stoneking, M. Dating the age of admixture via wavelet transform analysis of genome-wide data. Genome Biol. 12, R19 (2011).
Arbogast, B., Edwards, S., Wakeley, J., Beerlie, P. & Slowinski, J. Estimating divergence times from molecular data on phylogenetic and population genetic timescales. Annu. Rev. Ecol. Syst. 33, 707–740 (2002).
Cann, R. L., Stoneking, M. & Wilson, A. C. Mitochondrial DNA and human evolution. Nature 325, 31–36 (1987).
Ingman, M., Kaessmann, H., Paabo, S. & Gyllensten, U. Mitochondrial genome variation and the origin of modern humans. Nature 408, 708–713 (2000).
Underhill, P. A. et al. Y chromosome sequence variation and the history of human populations. Nature Genet. 26, 358–361 (2000).
Vigilant, L., Stoneking, M., Harpending, H., Hawkes, K. & Wilson, A. C. African populations and the evolution of human mitochondrial DNA. Science 253, 1503–1507 (1991).
Lohmueller, K. E., Bustamante, C. D. & Clark, A. G. Methods for human demographic inference using haplotype patterns from genomewide single-nucleotide polymorphism data. Genetics 182, 217–231 (2009).
Mellars, P. Going east: new genetic and archaeological perspectives on the modern human colonization of Eurasia. Science 313, 796–800 (2006).
Schaffner, S. F. et al. Calibrating a coalescent simulation of human genome sequence variation. Genome Res. 15, 1576–1583 (2005).
Prugnolle, F., Manica, A. & Balloux, F. Geography predicts neutral genetic diversity of human populations. Curr. Biol. 15, R159–R160 (2005).
Stoneking, M. Human origins. The molecular perspective. EMBO Rep. 9 (Suppl. 1), 46–50 (2008).
Lahr, M. & Foley, R. Multiple dispersals and modern human origins. Evol. Anthropol. 3, 48–60 (1994).
Grun, R. et al. U-series and ESR analyses of bones and teeth relating to the human burials from Skhul. J. Hum. Evol. 49, 316–334 (2005).
Lahr, M. M. & Foley, R. Multiple dispersals and modern human origins. Evol. Anthropol. 3, 48–60 (1994).
Gray, R. D., Drummond, A. J. & Greenhill, S. J. Language phylogenies reveal expansion pulses and pauses in Pacific settlement. Science 323, 479–483 (2009).
Kirch, P. Peopling of the Pacific: a holistic anthropological perspective. Annu. Rev. Anthropol. 39, 131–148 (2010).
Donohue, M. & Denham, T. Farming and language in Island Southeast Asia. Curr. Anthropol. 51, 223–256 (2010).
Terrell, J. in Lapita: Ancestors and Descendants (eds Sheppard, P., Thomas, T. & Summerhayes, G.) 255–269 (Publishing Press Ltd, Auckland, 2009).
Kayser, M. The human genetic history of Oceania: near and remote views of dispersal. Curr. Biol. 20, R194–R201 (2010).
Kayser, M. et al. Melanesian and Asian origins of Polynesians: mtDNA and Y chromosome gradients across the Pacific. Mol. Biol. Evol. 23, 2234–2244 (2006).
Soares, P. et al. Ancient voyaging and Polynesian origins. Am. J. Hum. Genet. 88, 239–247 (2011).
Friedlaender, J. S. et al. The genetic structure of Pacific Islanders. PLoS Genet. 4, e19 (2008).
Kayser, M. et al. Genome-wide analysis indicates more Asian than Melanesian ancestry of Polynesians. Am. J. Hum. Genet. 82, 194–198 (2008).
Chaubey, G. et al. Population genetic structure in Indian Austroasiatic speakers: the role of landscape barriers and sex-specific admixture. Mol. Biol. Evol. 28, 1013–1024 (2011).
Haak, W. et al. Ancient DNA from European early neolithic farmers reveals their near eastern affinities. PLoS Biol. 8, e1000536 (2010).
Haak, W. et al. Ancient DNA from the first European farmers in 7500-year-old Neolithic sites. Science 310, 1016–1018 (2005).
Sampietro, M. L. et al. Palaeogenetic evidence supports a dual model of Neolithic spreading into Europe. Proc. Biol. Sci. 274, 2161–2167 (2007).
Bramanti, B. et al. Genetic discontinuity between local hunter-gatherers and central Europe's first farmers. Science 326, 137–140 (2009).
Fagundes, N. J., Kanitz, R. & Bonatto, S. L. A reevaluation of the Native American mtDNA genome diversity and its bearing on the models of early colonization of Beringia. PLoS ONE 3, e3157 (2008).
Hubbe, M., Neves, W. A. & Harvati, K. Testing evolutionary and dispersion scenarios for the settlement of the new world. PLoS ONE 5, e11105 (2010).
Kitchen, A., Miyamoto, M. M. & Mulligan, C. J. A three-stage colonization model for the peopling of the Americas. PLoS ONE 3, e1596 (2008).
Mulligan, C. J., Kitchen, A. & Miyamoto, M. M. Updated three-stage model for the peopling of the Americas. PLoS ONE 3, e3199 (2008).
Ray, N. et al. A statistical evaluation of models for the initial settlement of the american continent emphasizes the importance of gene flow with Asia. Mol. Biol. Evol. 27, 337–345 (2010).
Cann, H. M. et al. A human genome diversity cell line panel. Science 296, 261–262 (2002).
Macaulay, V. et al. Single, rapid coastal settlement of Asia revealed by analysis of complete mitochondrial genomes. Science 308, 1034–1036 (2005).
Thangaraj, K. et al. Reconstructing the origin of Andaman Islanders. Science 308, 996 (2005).
Gunnarsdottir, E. D., Li, M., Bauchet, M., Finstermeier, K. & Stoneking, M. High-throughput sequencing of complete human mtDNA genomes from the Philippines. Genome Res. 21, 1–11 (2011).
Endicott, P. et al. The genetic origins of the Andaman Islanders. Am. J. Hum. Genet. 72, 178–184 (2003).
Forster, P. Ice Ages and the mitochondrial DNA chronology of human dispersals: a review. Phil. Trans. R. Soc. Lond. B 359, 255–264 (2004).
Cordaux, R. & Stoneking, M. South Asia, the Andamanese, and the genetic evidence for an “early” human dispersal out of Africa. Am. J. Hum. Genet. 72, 1586–1590; author reply 1590–1593 (2003).
The HUGO Pan-Asian SNP Consortium. Mapping human genetic diversity in Asia. Science 326, 1541–1545 (2009).
Wall, J. D., Lohmueller, K. E. & Plagnol, V. Detecting ancient admixture and estimating demographic parameters in multiple human populations. Mol. Biol. Evol. 26, 1823–1827 (2009).
Krause, J. From genes to genomes: what is new in ancient DNA? MGfU 19, 11–33 (2010).
Andrews, R. M. et al. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nature Genet. 23, 147 (1999).
We thank A. Briggs, B. Pakendorf and S. Pääbo for helpful comments. The work of the authors is supported by the Max Planck Society (M.S.) and the University of Tübingen, Germany (J.K.).
The authors declare no competing financial interests.
An international project with the goal of identifying genetic similarities and differences among human populations. The project has made large amounts of data publicly available.
Gene flow between two (or more) groups that have been separated for a long enough period of time to be genetically distinct.
- Demographic history
The history of events that influence the genetic structure of a population, including population size changes, divergence from other populations and migration (gene flow).
- SNP arrays
Microarrays that are used to simultaneously genotype several thousand to several hundred thousand SNPs for a single sample.
Modern humans, their fossil ancestors, and extinct relatives thereof, up to (but not including) chimpanzees.
Archaic hominins represented by fossil remains from Denisova Cave in southern Siberia; genome sequence data indicate that Denisovans are a sister group to Neanderthals.
The Saqqaq culture is the archaeological designation of the earliest culture of West and South East Greenland. A 4,000-year-old native Greenlander from the Saqqaq culture, whose hair sample was preserved in permafrost, was used to obtain the first genome sequence from an ancient modern human.
- Endogenous DNA
In the ancient DNA field, endogenous DNA usually refers to the original DNA from the actual organism that was sampled. In some publications, endogenous DNA includes the microbial DNA that is common to most ancient samples versus exogenous DNA that is brought onto or into the sample after excavation.
- Nucleotide misincorporations
Erroneous incorporations of nucleotides during the synthesis of the complementary DNA strand by a polymerase (for example, during PCR) that are caused by chemical modifications of the template nucleotides. For example, deamination of cytosine leads to uracil, which is read by the DNA polymerase as thymine and as a consequence instead of a guanine an adenine is incorporated into the complementary strand.
- Sequencing library
This consists of DNA samples that have been prepared for high-throughput DNA sequencing by adding artificial oligonucleotides to both ends of the template molecules. The adaptors can be used to bind the DNA to a surface and clonally amplify each molecule before or during high-throughput DNA sequencing.
- Post-mortem chemical damage
Chemical modifications to DNA that happen after the death of the organism: for example, hydrolytic deamination of cytosine.
- Cytosine deamination
In the context of ancient DNA, a post-mortem hydrolytic chemical reaction that changes cytosine to uracil, releasing ammonia in the process.
- Ascertainment bias
Sampling bias that arises from how SNPs are chosen for inclusion on SNP arrays; SNPs that are known to be polymorphic in a particular population will overestimate genetic variation in that population relative to other populations.
- Hybridization capture
A method that allows selective capture of genomic regions of interest from a complex DNA sample before DNA sequencing. It is based on hybridization between DNA fragments in the sample and chosen 'bait' sequences.
Geological epoch that spans the time period from about 2.5 million years ago to 12,000 years ago.
- Unsupervised analyses
Analyses that are done at the individual instead of the population level and do not require that population labels are applied to individuals.
- Ancestry components
A pre-defined number of subgroups with distinctive allele frequencies, inferred from genome-wide data, which are then used to assign the ancestry of each individual without specifying the population to which the individual belongs.
- Model-based analyses
Analyses that specify demographic models, investigate which demographic model best fits the genetic data and infer parameters of interest (such as population size changes, divergence times and migration events) for the best-fitting model.
- Summary statistics
Statistics that summarize various aspects of genetic data, such as heterozygosity (for within population variation) or FST values (for between population variation). Summary statistics are conventionally used to investigate the fit of demographic models to the actual genetic data.
The combined Australia–New Guinea landmass that existed periodically during cold periods in the Pleistocene, including during the initial colonization of Australia and New Guinea about 50,000 years ago, up until rising sea levels separated Australia from New Guinea about 8,000 years ago.
A large island in the Pacific that politically is part of Papua New Guinea but geographically is part of the main Solomon Islands chain.
The most geographically widespread family of languages, extending from Taiwan through mainland and island southeast Asia, Near Oceania, Remote Oceania and even Madagascar.
- Near Oceania
Refers to New Guinea and nearby offshore islands, including the main Solomon Islands chain (excluding Santa Cruz); Near Oceania was first colonized by humans at least 40,000 years ago, whereas Remote Oceania (Santa Cruz and all islands to the east) was only colonized by humans beginning about 3,200 years ago.
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Stoneking, M., Krause, J. Learning about human population history from ancient and modern genomes. Nat Rev Genet 12, 603–614 (2011). https://doi.org/10.1038/nrg3029
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