Sequence Evolution of Mitochondrial DNA in Humans and Chimpanzees: Control Region and a Protein-Coding Region

  • Thomas D. Kocher
  • Allan C. Wilson


Complete primary structures for the major non-coding region of 13 human and two chimpanzee mitochondrial DNAs (mtDNAs) were determined by direct sequencing via the polymerase chain reaction and compared to published sequences for one other human and two other chimpanzees. The human mtDNAs were chosen to represent the deepest branches found in a genealogical tree relating the restriction maps of 182 types of mtDNA. With the four chimpanzee sequences as outgroups, it was possible to place a root on the tree relating the human sequences. This root is consistent with the idea of an African origin for human mtDNA but does not rule out alternative hypotheses. Our sequences confirm a previous finding that the probability of substitution varies greatly among sites in the control region, some sites being so variable that they have probably changed many times since chimpanzees and humans had a common ancestor. In addition, our results show that the pattern of substitution in the control region has diverged since chimpanzees and humans had a common ancestor. These two observations may help to explain why it is hard to root the human tree with chimpanzee sequences as well as to determine the time of common ancestry for humans using the control region. Therefore, sequences were also obtained for a more slowly-evolving part of mtDNA, viz an 896-bp segment which includes parts of the genes for NADH dehydrogenase subunits 4 and 5. They show that the extent of divergence among humans in this segment of mtDNA is less than 3/79 of that between humans and chimpanzees. This result reinforces estimates based on restriction mapping that the last common ancestor of the humans sampled existed less than 200,000 years ago.


Control Region African Origin NADH Dehydrogenase Subunit Mitochondrial Control Region Conserve Sequence Block 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Cann RL, Stoneking M, Wilson AC (1987) Mitochondrial DNA and human evolution. Nature 325: 31–36PubMedCrossRefGoogle Scholar
  2. 2.
    Cavalli-Sforza LL, Piazza A, Menozzi P, Mountain J (1988) Reconstruction of human evolution: Bringing together genetic, archaeological, and linguistic data. Proc Natl Acad Sci USA 85: 6002–6006PubMedCrossRefGoogle Scholar
  3. 3.
    Nei M, Livshits G (1989) Genetic relationships of Europeans, Asians and Africans and the origin of modern Homo sapiens. Hum Hered 39: 276–281PubMedCrossRefGoogle Scholar
  4. 4.
    Vigilant L, Pennington R, Harpending H, Kocher TD, Wilson AC (1989) Mitochondrial DNA sequences in single hairs from a southern African population. Proc Natl Acad Sci USA 86: 9350–9354PubMedCrossRefGoogle Scholar
  5. 5.
    Horai S, Hayasaka K (1990) Intraspecific nucleotide sequence differences in the major noncoding region of human mitochondrial DNA. Am J Hum Genet 46: 828–842PubMedGoogle Scholar
  6. 6.
    Stringer CB, Andrews P (1988) Genetic and fossil evidence for the origin of modern humans. Science 239: 1263–1268PubMedCrossRefGoogle Scholar
  7. 7.
    Maynard Smith J (1989) Evolutionary genetics. Oxford University Press, New YorkGoogle Scholar
  8. 8.
    Wilson AC, Cann RL, Carr SM, George M, Gyllensten UB, Helm-Bychowski KM, Higuchi RG, Palumbi SR, Prager EM, Sage RD, Stoneking M (1985) Mitochondrial DNA and two perspectives on evolutionary genetics. Biol J Linn Soc 26: 375–400CrossRefGoogle Scholar
  9. 9.
    Takahata N (1990) A simple genealogical structure of strongly balanced allelic lines and trans–species evolution of polymorphism. Proc Natl Acad Sci USA 87: 2419–2423PubMedCrossRefGoogle Scholar
  10. 10.
    Ferris SD, Brown WM, Davidson WS, Wilson AC (1981) Extensive polymorphism in the mitochondrial DNA of apes. Proc Natl Acad Sci USA 78: 6319–6323PubMedCrossRefGoogle Scholar
  11. 11.
    Wilson AC, Stoneking M, Cann RL, Prager EM, Ferris SD, Wrischnik LA, Higuchi RG (1987) Mitochondrial clans and the age of our common mother. In: Vogel F, Sperling K (eds) Human Genetics. Springer, Berlin, pp 158–164CrossRefGoogle Scholar
  12. 12.
    Foran DR, Hixson JE, Brown WM (1988) Comparisons of ape and human sequences that regulate mitochondrial DNA transcription and D–loop DNA synthesis. Nucleic Acids Res 16: 5841–5861PubMedCrossRefGoogle Scholar
  13. 13.
    Wilson AC, Zimmer EA, Prager EM, Kocher TD (1989) Restriction mapping in the molecular systematics of mammals. In: Fernholm B, Bremver K, Jornvall H (eds) The hierarchy of life. Elsevier Science, Amsterdam, pp 407–419Google Scholar
  14. 14.
    Stoneking M, Bhatia K, Wilson AC (1986) Rate of sequence divergence estimated from restriction maps of mitochondrial DNAs from Papua New Guinea. Cold Spring Harbor Symp Quant Biol 51: 433–439PubMedGoogle Scholar
  15. 15.
    Stoneking M, Wilson AC (1989) Mitochondrial DNA. In: Hill AVS, Serjeantson SW (eds) The colonization of the Pacific. A genetic trail. Oxford University Press, Oxford, pp 215–245Google Scholar
  16. 16.
    Brown WM, Prager EM, Wang A, Wilson AC (1982) Mitochondrial DNA sequences of primates: Tempo and mode of evolution. J Mol Evol 18: 225–239PubMedCrossRefGoogle Scholar
  17. 17.
    Hayasaka K, Gojobori T, Horai S (1988) Molecular phylogeny and evolution of primate mitochondrial DNA. Mol Biol Evol 5: 626–644PubMedGoogle Scholar
  18. 18.
    Wilson AC, Ochman H, Prager EM (1987) Molecular time scale for evolution. Trends Genet 3: 241–247CrossRefGoogle Scholar
  19. 19.
    Hasegawa M, Kishino H, Hayasaka K Horai S (1990) Mitochondrial DNA evolution in primates. J Mol Evol 31: 113–121PubMedCrossRefGoogle Scholar
  20. 20.
    Stoneking M, Jorde LB, Bhatia K, Wilson AC (1990) Geographic variation in human mitochondrial DNA from Papua New Guinea. Genetics 124: 717 — 733PubMedGoogle Scholar
  21. 21.
    Anderson S, Bankier AT, Barrell BG, de Bruijn MHL, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, Schreier PH, Smith AJH, Staden R, Young IG (1981) Sequence and organization of the human mitochondrial genome. Nature 290: 457–465Google Scholar
  22. 22.
    Greenberg BD, Newbold JE, Sugino A (1983) Intraspecific nucleotide sequence variability surrounding the origin of replication in human mitochondrial DNA. Gene 21: 33–49PubMedCrossRefGoogle Scholar
  23. 23.
    White TJ, Arnheim N, Erlich HA (1989) The polymerase chain reaction. Trends Genet 5: 185–189PubMedCrossRefGoogle Scholar
  24. 24.
    Kocher TD, Thomas WK, Meyer A, Edwards SV, Paabo S, Villablanca FX, Wilson AC (1989) Dynamics of mitochondrial DNA evolution in animals: Amplification and sequencing with conserved primers. Proc Natl Acad Sci USA 86: 6196–6200PubMedCrossRefGoogle Scholar
  25. 25.
    Maniatis T, Fritsch EF, Sambrook J (1982) Molecular cloning. Cold Spring Harbor Laboratory, Cold Spring Harbor, New YorkGoogle Scholar
  26. 26.
    Gyllensten UB, Erlich HA (1988) Generation of single-stranded DNA by the polymerase chain reaction and its application to direct sequencing of the HLA-DQA locus. Proc Natl Acad Sci USA 85: 7652–7656PubMedCrossRefGoogle Scholar
  27. 27.
    Swofford DL (1989) PAUP: Phylogenetic analysis using parsimony, version 3. 0b. Illinois Natural History Survey, Champaign, IllinoisGoogle Scholar
  28. 28.
    Felsenstein J (1985) Confidence limits on phylogenies: An approach using the bootstrap. Evolution 39: 783–791CrossRefGoogle Scholar
  29. 29.
    Felsenstein J (1989) PHYLIP 3.2 manual. University of California Herbarium, Berkeley, CaliforniaGoogle Scholar
  30. 30.
    Saitou N, Nei M (1987) The neighbor-joining method. Mol Biol Evol 4: 406–425PubMedGoogle Scholar
  31. 31.
    Anderson S, de Bruijn MHL, Coulson AR, Eperon IC, Sanger F, Young IG (1982) Complete sequence of bovine mitochondrial DNA. J Mol Biol 156: 683–717PubMedCrossRefGoogle Scholar
  32. 32.
    Southern SO, Southern PJ, Dizon AE (1988) Molecular characterization of a cloned dolphin mitochondrial genome. J Mol Evol 28: 32–42PubMedCrossRefGoogle Scholar
  33. 33.
    Chang DD, Clayton DA (1984) Precise identification of individual promoters for transcription of each strand of human mitochondrial DNA. Cell 36: 635–643PubMedCrossRefGoogle Scholar
  34. 34.
    DeSalle R, Freedman T, Prager EM, Wilson AC (1987) Tempo and mode of sequence evolution in mitochondrial DNA of Hawaiian Drosophila. J Mol Evol 26: 157–164PubMedCrossRefGoogle Scholar
  35. 35.
    Groube L, Chappell J, Muke J, Price D (1986) A 40,000-year-old human occupation site at Huon Peninsula, Papua New Guinea. Nature 324: 453–455PubMedCrossRefGoogle Scholar
  36. 36.
    Roberts RG, Jones R, Smith MA (1990) Thermoluminescence dating of a 50,000-year- old human occupation site in northern Australia. Nature 345: 153–156CrossRefGoogle Scholar
  37. 37.
    Aquadro CF, Greenberg BD (1983) Human mitochondrial DNA variation and evolution. Genetics 103: 287–312PubMedGoogle Scholar
  38. 38.
    Uzzell T, Corbin KW (1971) Fitting discrete probability distributions to evolutionary events. Science 172: 1089–1096PubMedCrossRefGoogle Scholar
  39. 39.
    Holmquist R, Goodman M, Conroy T, CzelusniakJ (1983) Spatial distribution of fixed mutations within genes coding for proteins. J Mol Evol 19: 437–448PubMedCrossRefGoogle Scholar
  40. 40.
    Bliss CI, Fisher RA (1953) Fitting the negative binomial distribution to biological data. Biometrics 9: 176–200CrossRefGoogle Scholar
  41. 41.
    Larson A, Wilson AC (1989) Patterns of ribosomal RNA evolution in salamanders. Mol Biol Evol 6: 131–154PubMedGoogle Scholar
  42. 42.
    Stoneking M, Cann RL (1989) African origin of human mitochondrial DNA. In: Mellars P, Stringer C (eds) The human revolution. Behavioural and biological perspectives on the origins of modern humans. Edinburgh University Press, Edinburgh, pp 17–30Google Scholar
  43. 43.
    Whittam TS, Clark AG, Stoneking M, Cann RL, Wilson AC (1986) Allelic variation in human mitochondrial genes based on patterns of restriction site polymorphism. Proc Natl Acad Sci USA 83: 9611–9615PubMedCrossRefGoogle Scholar
  44. 44.
    Tajima F (1989) Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123: 585–595PubMedGoogle Scholar

Copyright information

© Springer-Verlag Tokyo 1991

Authors and Affiliations

  • Thomas D. Kocher
    • 1
    • 2
  • Allan C. Wilson
    • 2
  1. 1.Department of ZoologyUniversity of New HampshireDurhamUSA
  2. 2.Division of Biochemistry and Molecular BiologyUniversity of CaliforniaBerkeleyUSA

Personalised recommendations