Skip to main content
SpringerLink
Log in

Mitochondrial DNA sequences of primates: Tempo and mode of evolution

  • Original Articles
  • Published:
Journal of Molecular Evolution Aims and scope Submit manuscript

Summary

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

mtDNA:

mitochondrial DNA

bp:

base pair

URF:

unidentified reading frame

References

  • 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 290:457–465

    Google Scholar 

  • Anderson S, de Bruijn MHL, Coulson AR, Eperon IC, Sanger F, Young IG (1982) The complete sequence of bovine mitochondrial DNA: conserved features of the mammalian mitochondrial genome. J Mol Biol (in press)

  • Attardi G, Cantatore P, Ching E, Crews S, Gelfand R, Merkel C, Montoya J, Ojala D (1980) The remarkable features of gene organization and expression of human mitochondrial DNA. In: Kroon AM, Saccone C (eds) The organization and expression of the mitochondrial genome. Elsevier/North Holland Biomedical Press, Amsterdam, pp 103–119

    Google Scholar 

  • Barrell BG, Anderson S, Bankier AT, de Bruijn MHL, Chen E, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, Schreier PH, Smith AJH, Staden R, Young IG (1980) Different patterns of codon recognition by mammalian mitochondrial tRNAs. Proc Natl Acad Sci USA 77:3164–3166

    Google Scholar 

  • Barrie PA, Jeffreys AJ, Scott AF (1981) Evolution of theβ-globin gene cluster in man and the primates. J Mol Biol 149:319–336

    Google Scholar 

  • Bibb MJ, Van Etten RA, Wright CT, Walberg MW, Clayton DA (1981) Sequence and gene organization of mouse mitochondrial DNA. Cell 26:167–180

    Google Scholar 

  • Brown WM (1980) Polymorphism in mitochondrial DNA of humans as revealed by restriction endonuclease analysis. Proc Natl Acad Sci USA 77:3605–3609

    Google Scholar 

  • Brown WM (1981) Mechanisms of evolution of animal mitochondrial DNA. Annals NY Acad Sci 361:119–134

    Google Scholar 

  • Brown WM, George M Jr, Wilson AC (1979) Rapid evolution of animal mitochondrial DNA. Proc Natl Acad Sci USA 76:1967–1971

    Google Scholar 

  • Brown WM, Vinograd J (1974) Restriction endonuclease cleavage maps of animal mitochondrial DNAs. Proc Natl Acad Sci USA 71:4617–4621

    Google Scholar 

  • Brues AM (1977) People and races. Macmillan, New York, pp 1–336

    Google Scholar 

  • Cann RL, Brown WM, Wilson AC (1982) Evolution of human mitochondrial DNA: Molecular, genetic and anthropological implications. Proc Sixth Internat Congress Human Genetics, Vol I, in press

  • Castora FJ, Arnheim N, Simpson MV (1980) Mitochondrial DNA polymorphism: Evidence that variants detected by restriction enzymes differ in nucleotide sequence rather than in methylation. Proc Natl Acad Sci USA 77:6415–6419

    Google Scholar 

  • Cedergren RJ, Sankoff D, LaRue B, Grosjean H (1981) The evolving tRNA molecule. CRC Crit Rev Biochem 11:35–103

    Google Scholar 

  • Clemmey H (1976) World's oldest animal traces. Nature 261:576–578

    Google Scholar 

  • Cocks GT, Wilson AC (1972) Enzyme evolution in the Enterobacteriaceae. J Bacteriol 110:793–802

    Google Scholar 

  • Cordell B, Bell G, Tischer E, DeNoto FM, Ullrich A, Pictet A, Rutter WJ, Goodman HM (1979) Isolation and characterization of a rat insulin gene. Cell 18:533–543

    Google Scholar 

  • Dayhoff MO (1973) Atlas of protein sequence and structure, Vol 5, Supp I. Nat Biomed Res Found, Georgetown Univ Med Center, Wash DC, p S-101

    Google Scholar 

  • Dayhoff MO (1976) Atlas of protein sequence and structure, Vol 5, Supp 2. Nat Biomed Res Found, Georgetown Univ Med Center, Wash DC, pp 283–284

    Google Scholar 

  • de Bruijn MHL, Schreier PH, Eperon IC, Barrell BG, Chen EY, Armstrong PW, Wong JFH, Roe BA (1980) A mammalian mitochondrial serine transfer RNA lacking the “dihydrouridine” loop and stem. Nucleic Acids Res 8:5213–5222

    Google Scholar 

  • Derancourt J, Lebor AS, Zuckerkandl E (1967) Séquence des acides aminés, séquence des nucléotides et évolution. Bull Soc Chim Biol 49:577–607

    Google Scholar 

  • De Vos WM, Bakker H, Saccone C, Kroon AM (1980) Further analysis of the type differences of rat liver mitochondrial DNA. Biochim Biophys Acta 607:1–9

    Google Scholar 

  • Efstratiadis A, Posakony JW, Maniatis T, Lawn RM, O'Connell C, Spritz RA, DeRiel JK, Forget BG, Weissman SM, Slightom JL, Blechl AE, Smithies O, Baralle FE, Shoulders CC, Proudfoot NJ (1980) The structure and evolution of the humanβ-globin gene family. Cell 21: 653–668

    Google Scholar 

  • Farris JS (1972) Estimating phylogenetic trees from distance matrices. Am Natur 106: 645–668

    Google Scholar 

  • Ferris SD, Wilson AC, Brown WM (1981a) Evolutionary tree for apes and humans based on cleavage maps of mitochondrial DNA. Proc Natl Acad Sci USA 78:2432–2436

    Google Scholar 

  • Ferris SD, Brown WM, Davidson WS, Wilson AC (1981b) Extensive polymorphism in the mitochondrial DNA of apes. Proc Natl Acad Sci USA 78:6319–6323

    Google Scholar 

  • Fitch WM (1980) Estimating the total number of nucleotide substitutions since the common ancestor of a pair of homologous genes: Comparison of several methods and three beta hemoglobin messenger RNAs. J Mol Evol 16:153–209

    Google Scholar 

  • Fitch WM, Margoliash E (1967) Construction of phylogenetic trees. Science 155:279–284

    Google Scholar 

  • Freese E, Yoshida A (1965) The role of mutations in evolution. In: Bryson V, Vogel HJ (eds) Evolving genes and proteins. Academic Press, New York, pp 341–355

    Google Scholar 

  • Goddard JM, Masters JN, Jones SS, Ashworth WD, Wolstenholme DR (1981) Nucleotide sequence variants ofRattus norvegicus mitochondrial DNA. Chromosoma 82:595–609

    Google Scholar 

  • Hanahan D, Meselson M (1980) Plasmid screening at high colony density. Gene 10:63–67

    Google Scholar 

  • Heckman JE, Sarnoff J, Alzner-DeWeerd B, Yin S, RajBhandary UL (1980) Novel features in the genetic code and codon reading patterns inNeurospora crassa mitochondria based on sequences of six mitochondrial tRNAs. Proc Natl Acad Sci USA 77:3159–3163

    Google Scholar 

  • Holmquist R (1972) Theoretical foundations for a quantitative approach to paleogenetics. Part I: DNA. J Mol Evol 1:115–133

    Google Scholar 

  • Holmquist R, Jukes TH, Moise H, Goodman M, Moore GW (1976) The evolution of the globin family genes: Concordance of stochastic and augmented maximum parsimony genetic distances forα hemoglobin,β hemoglobin and myoglobin phylogenies. J Mol Biol 105:39–74

    Google Scholar 

  • Holmquist R, Pearl D (1980) Theoretical foundations for quantitative paleogenetics. Part III: The molecular divergence of nucleic acids and proteins for the case of genetic events of unequal probability. J Mol Evol 16:211–267

    Google Scholar 

  • Jukes TH (1980) Silent nucleotide substitutions and the molecular evolutionary clock. Science 210:973–978

    Google Scholar 

  • Jukes TH (1981) Amino acid codes in mitochondria as possible clues to primitive codes. J Mol Evol 18:15–17

    Google Scholar 

  • Jukes TH, Cantor CR (1969) Evolution of protein molecules. In: Munro HN (ed) Mammalian protein metabolism, Vol III, Academic Press, New York, pp 21–132

    Google Scholar 

  • Kimura M (1981) Possibility of extensive neutral evolution under stabilizing selection with special reference to nonrandom usage of synonymous codons. Proc Natl Acad Sci USA 78:5773–5777

    Google Scholar 

  • Kluge AG (1982) Reclassification of the great apes. In: Ciochon RL, Corruccini RS (eds) New interpretations of ape and human ancestry. Plenum Press, New York, in press

    Google Scholar 

  • Köchel HG, Lazarus CM, Basak N, Küntzel H (1981) Mitochondrial tRNA gene clusters inAspergillus nidulans: Organization and nucleotide sequence. Cell 23:625–633

    Google Scholar 

  • Martin NC, Miller D, Hartley J, Moynihan P, Donelson JE (1980) The tRNA SerAGY and tRNA ArgCGY genes form a gene cluster in yeast mitochondrial DNA. Cell 19:339–343

    Google Scholar 

  • Martin SL, Zimmer EA, Davidson WS, Wilson AC, Kan YW (1981) The untranslated regions ofβ-globin mRNA evolve at a functional rate in higher primates. Cell 25:737–741

    Google Scholar 

  • Maxam AM, Gilbert W (1980) Sequencing end-labeled DNA with base-specific chemical cleavages. Meth Enzymology 65:499–560

    Google Scholar 

  • Nichols BP, Miozzari GF, Van Cleemput M, Bennett GN, Yanofsky C (1980) Nucleotide sequences of the trp G regions ofEscherichia coli, Shigella dysenteriae, Salmonella typhimurium andSerratia marcescens. J Mol Biol 142:503–517

    Google Scholar 

  • Perler F, Efstratiadis A, Lomedico P, Gilbert W, Kolodner R, Dodgson J (1980) The evolution of genes: The chicken preproinsulin gene. Cell 20: 555–566

    Google Scholar 

  • Pilbeam D (1979) Recent finds and interpretations of Miocene hominoids. Ann Rev Anthrop 8:333–352

    Google Scholar 

  • Romer AS (1966) Vertebrate paleontology. Univ of Chicago, Chicago, pp 1–468

    Google Scholar 

  • Saccone C, Cantatore P, Gadaleta G, Gallerani R, Lanave C, Pepe G, Kroon AM (1981) The nucleotide sequence of the large ribosomal RNA gene and the adjacent tRNA genes from rat mitochondria. Nucleic Acids Res 9:4139–4148

    Google Scholar 

  • Sarich VM, Wilson AC (1967) Immunological time scale for hominid evolution. Science 158:1200–1203

    Google Scholar 

  • Singer CE, Smith GR (1972) Histidine regulation inSalmonella typhimurium. XIII. Nucleotide sequence of histidine transfer ribonucleic acid. J Biol Chem 247:2989–3000

    Google Scholar 

  • Sinha NK, Haimes MD (1981) Molecular mechanisms of substitution mutagenesis, J Biol Chem 256:10671–10683

    Google Scholar 

  • Smith HO (1980) Recovery of DNA from gels. Meth Enzymology 65:371–380

    Google Scholar 

  • Sprinzl M, Grueter F, Spelzhaus A, Gauss DH (1980) Compilation of tRNA sequences. Nucleic Acids Res 8:r1-r22

    Google Scholar 

  • Staden R (1980) A computer program to search for tRNA genes. Nucleic Acids Res 8:817–825

    Google Scholar 

  • Steel RGD, Torrie JH (1960) Principles and procedures of statistics-with special reference to the biological sciences. McGraw-Hill, New York, pp 1–481

    Google Scholar 

  • Topal MD, Fresco JR (1976) Complementary base pairing and the origin of substitution mutations. Nature 263:285–289

    Google Scholar 

  • Walberg MW, Clayton DA (1981) Sequence and properties of the human KB cell and mouse L cell D-loop regions of mitochondrial DNA. Nucleic Acids Res 9:5411–5421

    Google Scholar 

  • Wilson AC, Carlson SS, White TJ (1977) Biochemical evolution. Annu Rev Biochem 46:573–639

    Google Scholar 

  • Zimmer EA (1980) Evolution of primate globin genes. PhD Thesis, Univ of California, Berkeley, pp 1–366

    Google Scholar 

Download references

Author information

Author notes

  1. Wesley M. Brown

    Present address: Division of Biological Sciences, University of Michigan, 48109, Ann Arbor, Michigan, USA

  2. Alice Wang

    Present address: Cetus Corporation, 600 Bancroft Way, 94710, Berkeley, California, USA

Authors and Affiliations

  1. Department of Biochemistry, University of California, 94720, Berkeley, California, USA

    Wesley M. Brown, Ellen M. Prager, Alice Wang & Allan C. Wilson

Authors
  1. Wesley M. Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ellen M. Prager
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alice Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Allan C. Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brown, W.M., Prager, E.M., Wang, A. et al. Mitochondrial DNA sequences of primates: Tempo and mode of evolution. J Mol Evol 18, 225–239 (1982). https://doi.org/10.1007/BF01734101

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01734101

Key words

Search

Navigation