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Mitochondrial genome variation and the origin of modern humans

A Corrigendum to this article was published on 29 March 2001


The analysis of mitochondrial DNA (mtDNA) has been a potent tool in our understanding of human evolution, owing to characteristics such as high copy number, apparent lack of recombination1, high substitution rate2 and maternal mode of inheritance3. However, almost all studies of human evolution based on mtDNA sequencing have been confined to the control region, which constitutes less than 7% of the mitochondrial genome. These studies are complicated by the extreme variation in substitution rate between sites, and the consequence of parallel mutations4 causing difficulties in the estimation of genetic distance and making phylogenetic inferences questionable5. Most comprehensive studies of the human mitochondrial molecule have been carried out through restriction-fragment length polymorphism analysis6, providing data that are ill suited to estimations of mutation rate and therefore the timing of evolutionary events. Here, to improve the information obtained from the mitochondrial molecule for studies of human evolution, we describe the global mtDNA diversity in humans based on analyses of the complete mtDNA sequence of 53 humans of diverse origins. Our mtDNA data, in comparison with those of a parallel study of the Xq13.3 region7 in the same individuals, provide a concurrent view on human evolution with respect to the age of modern humans.

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Figure 1: The relationship between linkage disequilibrium, measured by |D ′| versus distance between nucleotide sites for all 53 complete human mtDNA genomes.
Figure 2: Neighbour-joining phylogram based on complete mtDNA genome sequences (excluding the D-loop).
Figure 3: Mismatch distributions of pairwise nucleotide differences between mtDNA genomes (excluding the D-loop).
Figure 4: Data matrices showing all informative nucleotide positions, in decreasing order of frequency.


  1. Olivio, P. D., Van de Walle, M. J., Laipis, P. J. & Hauswirth, W. W. Nucleotide sequence evidence for rapid genotypic shifts in the bovine mitochondrial DNA D-loop. Nature 306, 400– 402 (1983).

    ADS  Article  Google Scholar 

  2. Brown, W. M., George, M. Jr & Wilson, A. C. Rapid evolution of animal mitochondrial DNA. Proc. Natl Acad. Sci. USA 76, 1967– 1971 (1979).

    ADS  CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. Giles, R. E., Blanc, H., Cann, H. M. & Wallace, D. C. Maternal inheritance of human mitochondrial DNA. Proc. Natl Acad. Sci. USA 77, 6715–6719 (1980).

    ADS  CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. Tamura, K. & Nei, M. Estimation of the number of nucleotide substitutions in the control region of mitochondrial DNA in humans and chimpanzees. Mol. Biol. Evol. 10, 512– 526 (1993).

    CAS  PubMed  Google Scholar 

  5. Maddison, D. R., Ruvolo, M. & Swofford, D. L. Geographic origins of human mitochondrial DNA: phylogenetic evidence from control region sequences. Syst. Biol. 41, 111–124 (1992).

    Article  Google Scholar 

  6. Torroni, A. et al. mtDNA analysis reveals a major late Paleolithic population expansion from southwestern to northeastern Europe. Am. J. Hum. Genet. 62, 1137–1152 ( 1998).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. Kaessmann, H., Heissig, F., von Haeseler, A. & Paabo, S. DNA sequence variation in a non-coding region of low recombination on the human X chromosome. Nature Genet. 22, 78 –81 (1999).

    CAS  Article  PubMed  Google Scholar 

  8. Strimmer, K. & von Haesseler, A. Quartet puzzling: a quartet maximum-likelihood method for reconstructing tree topologies. Mol. Biol. Evol. 13, 964–969 (1996).

    CAS  Article  Google Scholar 

  9. Sarich, V. M. & Wilson, A. C. Generation time and genomic evolution in primates. Science 179, 1144– 1147 (1973).

    ADS  CAS  Article  PubMed  Google Scholar 

  10. Andrews, P. Evolution and environment in the Hominoidea. Nature 360, 641–646 (1992).

    ADS  CAS  Article  PubMed  Google Scholar 

  11. Kumar, S. & Hedges, S. B. A molecular timescale for vertebrate evolution. Nature 392, 917– 920 (1998).

    ADS  CAS  Article  PubMed  Google Scholar 

  12. Awadalla, P., Eyre-Walker, A. & Smith, J. M. Linkage disequilibrium and recombination in hominid mitochondrial DNA. Science 286, 2524– 2525 (1999).

    CAS  Article  PubMed  Google Scholar 

  13. Eyre-Walker, A., Smith, N. H. & Smith, J. M. How clonal are human mitochondria? Proc. R. Soc. Lond. B 266, 477–483 (1999).

    CAS  Article  Google Scholar 

  14. Kumar, S., Hedrick, P. & Stoneking, M. Questioning evidence for recombination in human mitochondrial DNA. Science 288, 1931 ( 2000).

    CAS  Article  PubMed  Google Scholar 

  15. Lewontin, R. C. The interaction of selection and linkage. I. General considerations; heterotic models. Genetics 49, 49– 67 (1964).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 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).

    ADS  CAS  Article  PubMed  Google Scholar 

  17. Cann, R. L., Stoneking, M. & Wilson, A. C. Mitochondrial DNA and human evolution. Nature 325, 31–36 ( 1987).

    ADS  CAS  Article  PubMed  Google Scholar 

  18. Wolpoff, M. H. in The Human Revolution: Behavioural and Biological Perspectives on the Origins of Modern Humans (eds Mellars, P. & Stringer, C.) 62–108 (Princeton Univ. Press, Princeton, New Jersey, 1989).

    Google Scholar 

  19. Horai, S., Hayasaka, K., Kondo, R., Tsugane, K. & Takahata, N. Recent African origin of modern humans revealed by complete sequences of hominoid mitochondrial DNAs. Proc. Natl Acad. Sci. USA 92, 532–536 ( 1995).

    ADS  CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. Ruvolo, M. et al. Mitochondrial COII sequences and modern human origins. Mol. Biol. Evol. 10, 1115–1135 (1993).

    CAS  PubMed  Google Scholar 

  21. Templeton, A. R. Human origins and analysis of mitochondrial DNA sequences. Science 255, 737 (1992).

    ADS  CAS  Article  PubMed  Google Scholar 

  22. Nei, M. Age of the common ancestor of human mitochondrial DNA. Mol. Biol. Evol. 9, 1176–1178 ( 1992).

    CAS  PubMed  Google Scholar 

  23. Saitou, N. & Nei, M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol. Biol. Evol. 4, 406–425 (1987).

    CAS  PubMed  Google Scholar 

  24. Zietkiewicz, E. et al. Genetic structure of the ancestral population of modern humans. J. Mol. Evol. 47, 146– 155 (1998).

    ADS  CAS  Article  PubMed  Google Scholar 

  25. Rogers, A. R. & Harpending, H. Population growth makes waves in the distribution of pairwise genetic differences. Mol. Biol. Evol. 9, 552–569 ( 1992).

    CAS  PubMed  Google Scholar 

  26. Fu, Y. X. & Li, W. H. Statistical tests of neutrality of mutations. Genetics 133, 693– 709 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Tajima, F. Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123, 585–595 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Rozas, J. & Rozas, R. DnaSP, DNA sequence polymorphism: an interactive program for estimating population genetics parameters from DNA sequence data. Comput. Appl. Biosci. 11, 621–625 (1995).

    CAS  PubMed  Google Scholar 

  29. Klein, R. G. The Human Career: Human Biological and Cultural Origins (Univ. Chicago Press, Chicago, 1989).

    Google Scholar 

  30. Reider, M. J., Taylor, S. L., Tobe, V. O. & Nickerson, D. A. Automating the identification of DNA variations using quality-based fluorescence re-sequencing: analysis of the human mitochondrial genome. Nucleic Acids Res. 26, 967–973 ( 1998).

    Article  Google Scholar 

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We thank M. Stoneking for his advice regarding the analysis of recombination, and L. Cavalli-Sforza, G. Destro-Bisol, L. Excoffier, T. Jenkins, K. Kidd, J. Kidd, G. Klein, R. Mahabeer, V. Nasidze, E. Poloni, H. Soodyall, M. Stoneking, M. Voevoda and S. Wells for scmples. This work was supported by grants from Swedish Natural Sciences Research Council and Beijer Foundation.

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Correspondence to Ulf Gyllensten.

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Ingman, M., Kaessmann, H., Pääbo, S. et al. Mitochondrial genome variation and the origin of modern humans. Nature 408, 708–713 (2000).

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