BACKGROUND: Recent analyses of de novo DNA mutations in modern humans have suggested a nuclear substitution rate that is approximately half that of previous estimates based on fossil calibration. This result has led to suggestions that major events in human evolution occurred far earlier than previously thought. RESULTS: Here, we use mitochondrial genome sequences from ten securely dated ancient modern humans spanning 40,000 years as calibration points for the mitochondrial clock, thus yielding a direct estimate of the mitochondrial substitution rate. Our clock yields mitochondrial divergence times that are in agreement with earlier estimates based on calibration points derived from either fossils or archaeological material. In particular, our results imply a separation of non-Africans from the most closely related sub-Saharan African mitochondrial DNAs (haplogroup L3) that occurred less than 62-95 kya. CONCLUSIONS: Though single loci like mitochondrial DNA (mtDNA) can only provide biased estimates of population divergence times, they can provide valid upper bounds. Our results exclude most of the older dates for African and non-African population divergences recently suggested by de novo mutation rate estimates in the nuclear genome.

Broad Institute of MIT and Harvard Cambridge MA 02142 USA

CAS MPS Joint Laboratory for Human Evolution and Archaeometry Institute of Vertebrate Paleontology and Paleoanthropology of Chinese Academy of Sciences Beijing 100044 P R China

Department of Anthropology Faculty of Science Masaryk University Vinařská 5 603 00 Brno

Department of Biology Emory University Atlanta GA 30322 USA

Department of Evolutionary Genetics Max Planck Institute for Evolutionary Anthropology Leipzig 04103 Germany

Department of Genetics Harvard Medical School Boston MA 02115 USA

Department of Prehistoric and Protohistoric Archaeology Institute for Archaeology and Cultural Anthropology University of Bonn Regina Pacis Weg 7 53113 Bonn Germany

Dipartimento di Biologia Evoluzionistica Università di Firenze Firenze Italy

Dipartimento di Scienze Archeologiche Università di Pisa via Galvani 1 56126 Pisa

Human Genetics Department Medical Faculty University of Tübingen 72070 Tübingen Germany

Institute for Archaeological Sciences University of Tübingen Rümelinstr 23 Tübingen Germany

Institute of Archaeology Academy of Science of the Czech Republic Kralovopolska 147 612 00 Brno Czech Republic

Laboratoire de Paléoanthropologie École Pratique des Hautes Études UMR 5199 PACEA CNRS Université de Bordeaux Bordeaux France

LVR Landesmuseum Bonn Bachstrasse 5 9 D 53115 Bonn Germany

Palaeogenetics Group Institute for Anthropology Johannes Gutenberg University Saarstrasse 21 D 55099 Mainz Germany

ShandongMuseum 11899 Jing 10th Road Jinan Shandong 250014 P R China

Università degli Studi di Siena Dip di Scienze Fisiche della Terra e dell'Ambiente U R Ecologia Preistorica Via Laterina 8 53100 Siena Italy

Università di Firenze Dipartimento di Scienze dell'Antichità Medioevo e Rinascimento e Linguistica Piazza Brunelleschi 3 4 50121 Firenze Italy

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Scally A, Durbin R. Revising the human mutation rate: implications for understanding human evolution. Nat Rev Genet. 2012;13:745–753. PubMed

Awadalla P, Gauthier J, Myers RA, Casals F, Hamdan FF, Griffing AR, Cote M, Henrion E, Spiegelman D, Tarabeux J, et al. Direct measure of the de novo mutation rate in autism and schizophrenia cohorts. American journal of human genetics. 2010;87:316–324. PubMed PMC

Consortium GP. A map of human genome variation from population-scale sequencing. Nature. 2010;467:1061–1073. PubMed PMC

Kong A, Frigge ML, Masson G, Besenbacher S, Sulem P, Magnusson G, Gudjonsson SA, Sigurdsson A, Jonasdottir A, Wong WS, et al. Rate of de novo mutations and the importance of father's age to disease risk. Nature. 2012;488:471–475. PubMed PMC

Roach JC, Glusman G, Smit AF, Huff CD, Hubley R, Shannon PT, Rowen L, Pant KP, Goodman N, Bamshad M, et al. Analysis of genetic inheritance in a family quartet by whole-genome sequencing. Science. 2010;328:636–639. PubMed PMC

Endicott P, Ho SY, Metspalu M, Stringer C. Evaluating the mitochondrial timescale of human evolution. Trends in ecology & evolution. 2009;24:515–521. PubMed

Mishmar D, Ruiz-Pesini E, Golik P, Macaulay V, Clark AG, Hosseini S, Brandon M, Easley K, Chen E, Brown MD, et al. Natural selection shaped regional mtDNA variation in humans. Proceedings of the National Academy of Sciences of the United States of America. 2003;100:171–176. PubMed PMC

Friedlaender J, Schurr T, Gentz F, Koki G, Friedlaender F, Horvat G, Babb P, Cerchio S, Kaestle F, Schanfield M, et al. Expanding Southwest Pacific mitochondrial haplogroups P and Q. Molecular biology and evolution. 2005;22:1506–1517. PubMed

Soares P, Ermini L, Thomson N, Mormina M, Rito T, Rohl A, Salas A, Oppenheimer S, Macaulay V, Richards MB. Correcting for purifying selection: an improved human mitochondrial molecular clock. American journal of human genetics. 2009;84:740–759. PubMed PMC

Krause J, Briggs AW, Kircher M, Maricic T, Zwyns N, Derevianko A, Paabo S. A complete mtDNA genome of an early modern human from Kostenki, Russia. Curr Biol. 2010;20:231–236. PubMed

Green RE, Malaspinas AS, Krause J, Briggs AW, Johnson PL, Uhler C, Meyer M, Good JM, Maricic T, Stenzel U, et al. A complete Neandertal mitochondrial genome sequence determined by high-throughput sequencing. Cell. 2008;134:416–426. PubMed PMC

Briggs AW, Stenzel U, Johnson PL, Green RE, Kelso J, Prufer K, Meyer M, Krause J, Ronan MT, Lachmann M, et al. Patterns of damage in genomic DNA sequences from a Neandertal. Proceedings of the National Academy of Sciences of the United States of America. 2007;104:14616–14621. PubMed PMC

Sawyer S, Krause J, Guschanski K, Savolainen V, Paabo S. Temporal patterns of nucleotide misincorporations and DNA fragmentation in ancient DNA. PloS one. 2012;7:e34131. PubMed PMC

Stoneking M, Krause J. Learning about human population history from ancient and modern genomes. Nature Reviews Genetics. 2011;12:603–614. PubMed

Bramanti B, Thomas MG, Haak W, Unterlaender M, Jores P, Tambets K, Antanaitis-Jacobs I, Haidle MN, Jankauskas R, Kind CJ, et al. Genetic Discontinuity Between Local Hunter-Gatherers and Central Europe's First Farmers. Science. 2009 PubMed

Henry-Gambier D. Les fossiles de Cro-Magnon (Les Eyzies-de-Tayac, Dordogne): Nouvelles donnees sur leur Position chronologique et leur attribution culturelle. Bull. et Mém. de la Société d’Anthropologie de Paris. 2002;14:89–112.

Briggs AW, Good JM, Green RE, Krause J, Maricic T, Stenzel U, Lalueza-Fox C, Rudan P, Brajkovic D, Kucan Z, et al. Targeted retrieval and analysis of five Neandertal mtDNA genomes. Science. 2009;325:318–321. PubMed

Richards MB, Macaulay VA, Bandelt HJ, Sykes BC. Phylogeography of mitochondrial DNA in western Europe. Ann Hum Genet. 1998;62:241–260. PubMed

Fenner JN. Cross-cultural estimation of the human generation interval for use in genetics-based population divergence studies. Am. J. Phys. Anthropol. 2005;128:415–423. PubMed

Sun JX, Helgason A, Masson G, Ebenesersdottir SS, Li H, Mallick S, Gnerre S, Patterson N, Kong A, Reich D, et al. A direct characterization of human mutation based on microsatellites. Nature genetics. 2012;44:1161–1165. PubMed PMC

Hobolth A, Dutheil JY, Hawks J, Schierup MH, Mailund T. Incomplete lineage sorting patterns among human, chimpanzee, and orangutan suggest recent orangutan speciation and widespread selection. Genome research. 2011;21:349–356. PubMed PMC

Andrews P, Cronin JE. The relationships of sivapithecus and ramapithecus and the evolution of the orangutan. Nature. 1982;297:541–546. PubMed

Meyer M, Kircher M, Gansauge MT, Li H, Racimo F, Mallick S, Schraiber JG, Jay F, Prufer K, de Filippo C, et al. A high-coverage genome sequence from an archaic Denisovan individual. Science. 2012;338:222–226. PubMed PMC

van Oven M, Kayser M. Updated comprehensive phylogenetic tree of global human mitochondrial DNA variation. Hum Mutat. 2009;30:E386–394. PubMed

Edgar RC. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic acids research. 2004;32:1792–1797. PubMed PMC

Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S. MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Molecular biology and evolution. 2011;28:2731–2739. PubMed PMC

Ingman M, Kaessmann H, Paabo S, Gyllensten U. Mitochondrial genome variation and the origin of modern humans. Nature. 2000;408:708–713. PubMed

Krause J, Fu Q, Good JM, Viola B, Shunkov MV, Derevianko AP, Paabo S. The complete mitochondrial DNA genome of an unknown hominin from southern Siberia. Nature. 2010;464:894–897. PubMed PMC

Fu Q, Meyer M, Gao X, Stenzel U, Burbano HA, Kelso J, Paabo S. DNA analysis of an early modern human from Tianyuan Cave, China. Proceedings of the National Academy of Sciences of the United States of America. 2013 PubMed PMC

Ermini L, Olivieri C, Rizzi E, Corti G, Bonnal R, Soares P, Luciani S, Marota I, De Bellis G, Richards MB, et al. Complete mitochondrial genome sequence of the Tyrolean Iceman. Curr Biol. 2008;18:1687–1693. PubMed

Gilbert MT, Kivisild T, Gronnow B, Andersen PK, Metspalu E, Reidla M, Tamm E, Axelsson E, Gotherstrom A, Campos PF, et al. Paleo-Eskimo mtDNA genome reveals matrilineal discontinuity in Greenland. Science. 2008;320:1787–1789. PubMed

Drummond AJ, Rambaut A. BEAST: Bayesian evolutionary analysis by sampling trees. BMC Evol Biol. 2007;7:214. PubMed PMC

Posada D. Using MODELTEST and PAUP* to select a model of nucleotide substitution. Curr Protoc Bioinformatics. 2003 Chapter 6, Unit 6 5. PubMed

Green RE, Briggs AW, Krause J, Prufer K, Burbano HA, Siebauer M, Lachmann M, Paabo S. The Neandertal genome and ancient DNA authenticity. EMBO J. 2009;28:2494–2502. PubMed PMC

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