Journal of Molecular Evolution

, Volume 30, Issue 2, pp 116–124 | Cite as

The biological equilibrium of base pairs

  • Peter Strazewski
Article

Summary

An inherent feature of double-stranded DNA is the possible replacement of any base pair by another one upon replication. A replication-dependent substitution mutation of a matched base pair requires the temporary formation of a mismatched base pair (mispair). A functionally complementary pair of mispairs is ascribed to each of the four types of substitution mutations. Provided that all types of mispairs can be formed, a dynamic biological equilibrium between the four matched base pairs must exist in all DNA, which is directly related to the formation and stability of the corresponding eight mispairs in vivo. Each nucleotide position in a genome can therefore be described as a system of six dynamic equilibria between the four matched base pairs. After a sufficient number of replications, these equilibrium states will express an overall mutation-selection balance for each individual base pair. In a thermodynamic context, the mispairs represent intermediate states on the transformation pathway between the matched base pairs. Catalysts change the stability and probability of formation of intermediate states. Mutagenic proteins are proposed as hypothetical substitution mutation catalysts in vivo. Functionally, they would be capable of recognizing a particular DNA sequence, tautomerizing a nucleotide base thereof, and hence efficiently inducing a specific misincorporation. Phenomenologically such catalysts would accelerate the rates of substitution mutations and provide pathways for directional mutation pressure.

Key words

Thermodynamic model of DNA base pairs Mutation-selection equilibrium Directional mutation pressure Optimons Rate of mutation Substitution mutations Mismatches Rare tautomers Tautomerizing proteins 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Beutler E, Gelbart T, Han J, Koziol JA, Beutler B (1989) Evolution of the genome and the genetic code: selection at the dinucleotide level by methylation and polyribonucleotide cleavage. Proc Natl Acad Sci USA 86:192–196PubMedGoogle Scholar
  2. Cairns J, Overbaugh J, Miller S (1988) The origin of mutants. Nature 335:142–145PubMedGoogle Scholar
  3. Charczuk R, Tamm C, Suri B, Bickle T (1986) An unusual base pairing between pyrimidine and pyridine nucleotides. Nucleic Acids Res 14:9530PubMedGoogle Scholar
  4. Dawkins R (1982) The extended phenotype. The gene as the unit of selection, ed 2 (1987). Oxford University Press, New York, pp 81–96Google Scholar
  5. Discussions about Cairns et al. (1988/1989) in Nature (1988) 335:112–113, 336:21–22, 336:525–528, in Nature (1989) 337: 119–120, 337:123–124Google Scholar
  6. Dohet C, Wagner R, Radman M (1985) Repair of defined single base-pair mismatches inEscherichia coli. Proc Natl Acad Sci USA 82:503–505Google Scholar
  7. Dover GA (1987) DNA turnover and the molecular clock. J Mol Evol 26:47–58PubMedGoogle Scholar
  8. Eigen M (1971) Selforganization of matter and the evolution of biological macromolecules. Naturwissenschaften 10:465–523Google Scholar
  9. Eigen M (1978) The hypercycle. Part B: the abstract hypercycle. Naturwissenschaften 65:7–41Google Scholar
  10. Eigen M, Schuster P (1977) The hypercycle. Part A: emergence of the hypercycle. Naturwissenschaften 11:541–565Google Scholar
  11. Eigen M, Schuster P (1978) The hypercycle. Part C: the realistic hypercycle. Naturwissenschaften 7:341–369Google Scholar
  12. Fowler RG, Schaaper RM, Glickman BW (1986) Characterization of mutational specificity within the lac-1 gene for a mutD5 mutator strain ofEscherichia coli defective in 3′-5′ exonuclease proofreading activity. J Bacteriol 167:130–137PubMedGoogle Scholar
  13. French DL, Laskov R, Scharff MD (1989) The role of somatic hypermutation in the generation of antibody diversity. Science 244:1152–1157PubMedGoogle Scholar
  14. Goodman MF, Branscomb EW (1986) DNA replication fidelity and base mispairing mutagenesis. In: Kirkwood TBL, Rosenberger RF, Galas DJ (eds) Accuracy in molecular processes. Chapman & Hall, London, New York, pp 191–232Google Scholar
  15. Gutman GA, Hatfield GW (1989) Nonrandom utilization of codon pairs inEscherichia coli. Proc Natl Acad Sci USA 86: 3699–3703PubMedGoogle Scholar
  16. Ikemura T (1985) Codon usage, tRNA content, and rate of synonymous substitution. In: Ohta T, Aoki K (eds) Population genetics and molecular evolution. Springer-Verlag, Berlin, pp 385–406Google Scholar
  17. Jukes T, Bhushan V (1986) Silent nucleotide substitutions and G+C content of some mitochondrial and bacterial genes. J Mol Evol 24:39–44PubMedGoogle Scholar
  18. Kimura M (1983) The neutral theory of molecular evolution. Cambridge University Press, LondonGoogle Scholar
  19. Kuchta RD, Benkovic P, Benkovic SJ (1988) Kinetic mechanism whereby DNA polymerase I (Klenow) replicates with high fidelity. Biochemistry 27:6716–6725PubMedGoogle Scholar
  20. Kunkel TA, Bebenek K (1988) Recent studies of the fidelity of DNA synthesis. Biochim Biophys Acta 951:1–15PubMedGoogle Scholar
  21. Ohno S (1988a) Codon preference is but an illusion created by the construction principle of coding sequences. Proc Natl Acad Sci USA 85:4378–4382PubMedGoogle Scholar
  22. Ohno S (1988b) Universal rule for coding sequence construction: TA/CG deficiency-TG/CT excess. Proc Natl Acad Sci USA 85:9630–9634PubMedGoogle Scholar
  23. Ollis DL, Brick P, Hamlin R, Xuong NG, Steitz TA (1985) Structure of large fragment ofEscherichia coli DNA polymerase I complexed with dTMP. Nature 313:762–766PubMedGoogle Scholar
  24. Schaaper RM, Danforth BN, Glickman BW (1986) Mechanisms of spontaneous mutagenesis. An analysis of the spectrum of spontaneous mutation in theEscherichia coli lac-1 gene. J Mol Biol 189:273–284PubMedGoogle Scholar
  25. Schaaper RM, Dunn RL (1987) Spectra of spontaneous mutations inEscherichia coli strains defective in mismatch correction. The nature of in-vivo DNA replication errors. Proc Natl Acad Sci USA 84:6220–6224PubMedGoogle Scholar
  26. Strazewski P (1988) Mispair formation in DNA can involve rare tautomeric forms in the template. Nucleic Acids Res 16: 9377–9398PubMedGoogle Scholar
  27. Strazewski P, Tamm C (1990) Replication experiments with nucleotide base analogues. Angew Chem 102 (in press)Google Scholar
  28. Sueoka N (1988) Directional mutation pressure and neutral molecular evolution. Proc Natl Acad Sci USA 85:2653–2657PubMedGoogle Scholar
  29. Tonegawa S (1988) How does an organism manage during its lifetime to respond to a huge number of different antigens. Angew Chem Int Ed Engl 27:1028–1039Google Scholar
  30. Topal MD, Fresco JR (1976) Complementary base pairing and the origin of substitution mutations. Nature 263:285–289PubMedGoogle Scholar
  31. Vogel H, Zuckerkandl E (1971) Randomness and “thermodynamics” of molecular evolution. In: Schoffeniels E (ed) Biochemical evolution and the origin of life. North-Holland. Amsterdam, pp 352–365Google Scholar
  32. Wolfe KH, Sharp PM, Li W-H (1989) Mutation rates differ among regions of the mammalian genome. Nature 337:283–285PubMedGoogle Scholar
  33. Zckerkandl E (1965) Remarques sur l'évolution des polynucléotides comparée à celle des polypeptides. Bull Soc Chim Biol 47:1729–1730PubMedGoogle Scholar
  34. Zckerkandl E (1987) On the molecular evolutionary clock. J Mol Evol 26:34–46PubMedGoogle Scholar
  35. Zuckerkandl E, Pauling L (1965) Molecules as documents of evolutionary history. J theoret Biol 8:357–366Google Scholar

Copyright information

© Springer-Verlag New York Inc. 1990

Authors and Affiliations

  • Peter Strazewski
    • 1
  1. 1.Institut für organische Chemie der UniversitätBaselSwitzerland

Personalised recommendations