Journal of Molecular Evolution

, Volume 18, Issue 4, pp 225–239

Mitochondrial DNA sequences of primates: Tempo and mode of evolution


  • Wesley M. Brown
    • Department of BiochemistryUniversity of California
  • Ellen M. Prager
    • Department of BiochemistryUniversity of California
  • Alice Wang
    • Department of BiochemistryUniversity of California
  • Allan C. Wilson
    • Department of BiochemistryUniversity of California
Original Articles

DOI: 10.1007/BF01734101

Cite this article as:
Brown, W.M., Prager, E.M., Wang, A. et al. J Mol Evol (1982) 18: 225. doi:10.1007/BF01734101


We cloned and sequenced a segment of mitochondrial DNA from human, chimpanzee, gorilla, orangutan, and gibbon. This segment is 896 bp in length, contains the genes for three transfer RNAs and parts of two proteins, and is homologous in all 5 primates. The 5 sequences differ from one another by base substitutions at 283 positions and by a deletion of one base pair. The sequence differences range from 9 to 19% among species, in agreement with estimates from cleavage map comparisons, thus confirming that the rate of mtDNA evolution in primates is 5 to 10 times higher than in nuclear DNA. The most striking new finding to emerge from these comparisons is that transitions greatly outnumber transversions. Ninety-two percent of the differences among the most closely related species (human, chimpanzee, and gorilla) are transitions. For pairs of species with longer divergence times, the observed percentage of transitions falls until, in the case of comparisons between primates and non-primates, it reaches a value of 45. The time dependence is probably due to obliteration of the record of transitions by multiple substitutions at the same nucleotide site. This finding illustrates the importance of choosing closely related species for analysis of the evolutionary process. The remarkable bias toward transitions in mtDNA evolution necessitates the revision of equations that correct for multiple substitutions at the same site. With revised equations, we calculated the incidence of silent and replacement substitutions in the two protein-coding genes. The silent substitution rate is 4 to 6 times higher than the replacement rate, indicating strong functional constraints at replacement sites. Moreover, the silent rate for these two genes is about 10% per million years, a value 10 times higher than the silent rate for the nuclear genes studied so far. In addition, the mean substitution rate in the three mitochondrial tRNA genes is at least 100 times higher than in nuclear tRNA genes. Finally, genealogical analysis of the sequence differences supports the view that the human lineage branched off only slightly before the gorilla and chimpanzee lineages diverged and strengthens the hypothesis that humans are more related to gorillas and chimpanzees than is the orangutan.

Key words

DNA sequencingTransitionsMultiplehit correctionsSilent substitutionsReplacement substitutionsTransfer RNAMutation pressureFunctional constraintsHominoid phylogenyStart codons



mitochondrial DNA


base pair


unidentified reading frame

Copyright information

© Springer-Verlag 1982