Journal of Molecular Evolution

, Volume 21, Issue 4, pp 346–350 | Cite as

Mammalian genes as molecular clocks?

  • Cecilia Lanave
  • Giuliano Preparata
  • Cecilia Saccone


In analyzing the silent nucleotide substitutions in some mammalian mitochondrial mRNA coding genes, we had found that the frequency of each of the four nucleotides in rat, mouse, and cow, but not in humans, is the same in the silent third codon position (Lanave C, Preparata G, Saccone C, Serio G (1984) J Mol Evol 20:86-93). Because our findings for these three species were compatible with a stationary Markov process for the evolution of nucleotide sequences, we applied such a model to calculate the effective evolutionary silent substitution rate (vs) and the divergence times among the species. In this paper we have analyzed the first and second codon positions in the same mammalian mitochondrial genes. We found that in the first and second codon positions the human mitochondrial genes satisfy the stationarity conditions. This has allowed us to use the stochastic model mentioned above to calculate the divergence times among mouse, rat, cow, and human. Furthermore, we have analyzed the silent substitution rate in one nuclear gene for these four mammals. We found that in this gene the effective silent substitution rate is about 3 times lower than in mitochondrial genes, and that humans are in this case stationary with respect to the other three mammals in the third codon position as well. Application of our Markov model to this latter gene yields divergence times consistent with our previous determinations.

Key words

Molecular evolution Evolution of mitochondrial genes Evolution of nuclear genes Stochastic Markov chain Monte Carlo Simulation 

Abbreviations used










milion years




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  1. Anderson S, Bankier AT, Barrell GB, 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 290:457–464CrossRefPubMedGoogle Scholar
  2. Anderson S, de Bruijn MHL, Coulson AR, Eperon IC, Sanger F, Young IG (1982) Complete sequence of bovine mitochondrial DNA. J Mol Biol 156:683–717CrossRefPubMedGoogle Scholar
  3. Bibb MJ, van Etten RA, Wright CT, Walberg MW, Clayton DA (1981) Sequence and gene organization of mouse mitochondrial DNA. Cell 26:167–180CrossRefPubMedGoogle Scholar
  4. Brown WM, George M Jr, Wilson AC (1979) Rapid evolution of animal mitochondrial DNA. Proc Natl Acad Sci USA 76: 1967–1971PubMedGoogle Scholar
  5. Brown WM, Prager EM, Wang A, Wilson AC (1982) Mitochondrial DNA sequences of primates: tempo and mode of evolution. J Mol Evol 18:225–239PubMedGoogle Scholar
  6. Cantatore P, De Benedetto C, Gadaleta G, Gallerani R, Kroon AM, Holtrop M, Lanave C, Pepe G, Quagliariello C, Saccone C, Sbisà E (1982) The nucleotide sequences of several tRNA genes from rat mitochondria: common features and relatedness to homologous species. Nucleic Acids Res 10:3279–3289PubMedGoogle Scholar
  7. Chang ACY, Cochet M, Cohen SN (1980) Structural organization of human genomic DNA encoding the pro-opiomelano-cortin peptide. Proc Natl Acad Sci USA 77:4890–4894Google Scholar
  8. Dayhoff MO (1978) In: Dayhoff MD (ed) Atlas of protein sequence and structure. Vol. 5, Suppl 3. National Biomedical Research Foundation, Silver Spring, Maryland, pp 1–414Google Scholar
  9. Drouin J, Goodman HM (1980) Most of the coding region of rat acth-beta-lph precursor gene lacks intevening sequences. Nature 288:610–613CrossRefPubMedGoogle Scholar
  10. Grosskopf R, Feldman H (1981) Analysis of a DNA segment from rat liver mitochondria containing the genes for the cytochrome oxidase subunits I, II and III, ATPase subunit 6 and several tRNA genes. curr Genet 4:151–158CrossRefGoogle Scholar
  11. Kobayashi M, Seki T, Yaginuma K, Koike K (1981) Nucleotide sequences of small ribosomal RNA and adjacent transfer RNA genes in rat mitochondrial DNA. Gene 16:297–307PubMedGoogle Scholar
  12. Koike K, Kobayashi M, Yaginuma K, Taira M, Yoshida E, Imai M (1982) Nucleotide sequence and evolution of the rat mitochondrial cytochrome b gene containing the ochre termination codon. Gene 20:177–185CrossRefPubMedGoogle Scholar
  13. Lanave C, Preparata G, Saccone C, Serio G (1984) A new method for calculating evolutionary substitution rates. J Mol Evol 20:86–93PubMedGoogle Scholar
  14. Miyata T, Hayashida H, Kikuno R, Hasegawa M, Kobayashi M, Koike K (1982) Molecular clock of silent substitution: at least six-fold preponderance of silent changes in mitochondrial genes over those in nuclear genes. J Mol Evol 19:28–35PubMedGoogle Scholar
  15. Nakanishi S, Taranishi Y, Watanabe Y, Notake Y, Noda M, Kakidani H, Jingami H, Numa S (1981) Isolation and characterization of the bovine corticotropin/beta lipotropin precursor gene. Eur J Biochem 115:429–438PubMedGoogle Scholar
  16. Notake M, Tobimatsu T, Watanabe Y, Takahashi H, Mishina M, Numa S (1983) Isolation and characterization of the mouse corticotropin-beta-lipotropin precursor gene and a related pseudogene. FEBS Lett 156:67–71CrossRefPubMedGoogle Scholar
  17. Parker RC, Watson RM (1977) Restriction endonuclease cleavage maps of rat and mouse mitochondrial DNAs. Nucleic Acids Res 4:1291–1299PubMedGoogle Scholar
  18. Pepe G, Holtrop M, Gadaleta G, Kroon AM, Cantatore P, Gallerani R, De Benedetto C, Quagliariello C, Sbisà E, Saccone C (1983) Non-random patterns of nucleotide substitutions and codon strategy in the mammalian mitochondrial genes coding for identified and unidentified reading frames. Biochem Int 6:553–563PubMedGoogle Scholar
  19. Saccone C, De Benedetto C, Gadaleta G, Lanave C, Pepe G, Sbisà E, Cantatore P, Gallerani R, Quagliariello C, Holtrop M, Kroon AM (1983) Studies on the evolutionary history of the mammalian mitochondrial genome. In: Nagley P, Linnane AW, Peacock WJ, Pateman JA (eds) Manipulation and expression of genes in eukaryotes. Academic Press, Sydney, in pressGoogle Scholar
  20. Sekiya T, Kobayashi M, Seki T, Koike K (1980) Nucleotide sequence of a cloned fragment of rat mitochondrial DNA containing the replication origin. Gene 11:53–62CrossRefPubMedGoogle Scholar
  21. Wilson AC, Carlson SS, White TJ (1977) Biochemical evolution. Annu Rev Biochem 46:573–639CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • Cecilia Lanave
    • 1
  • Giuliano Preparata
    • 2
  • Cecilia Saccone
    • 1
  1. 1.Centro CNR Mitocondri e Metabolismo EnergeticoInstituto di Chimica BiologicaBariItaly
  2. 2.Dipartimento di Fisica, UniversitàBariItaly

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