Quantitative Analysis of Selection and Mutation in Self-Replicating RNA

  • Christof K. Biebricher
  • M. Eigen
  • William C. GardinerJr.
Part of the NATO ASI Series book series (NSSB, volume 263)


The neo-Darwinian theory, based on Mendelian genetics1, brought the first quantitative analysis of evolution in the first half of this century. It was often claimed, however, that while Darwinian theory is excellent for explaining natural phenomena, it fails to make quantitative predictions. Given the complexity of biological expression of highly sophisticated living organisms, selective or fitness values can of course only be determined from the outcome of selection. Furthermore, many assumptions have to be made to calculate gene frequencies and their alteration, and in many cases the assumptions are not realistic in the ever-changing environments.


Mutation Rate Mutant Frequency Exponential Growth Phase Replication Rate Fitness Landscape 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    T. Dobzhansky, F. J. Ayala, G. L. Stebbins and J. W. Valentine, Evolution, Freeman, San Francisco (1977).Google Scholar
  2. 2.
    M. Eigen, Selforganization of matter and the evolution of biological macromolecules, Naturwissenschaften 58: 465 (1971).ADSCrossRefGoogle Scholar
  3. 3.
    D. R. Mills, R. L. Peterson and S. Spiegelman, An extracellular Darwinian experiment with a self-duplicating nucleic acid molecule, Proc. Nat. Acad. Sci. USA 58: 217 (1967).ADSCrossRefGoogle Scholar
  4. 4.
    L. E. Orgel, Selection in vitro, Proc. R. Soc. Lond. B 205: 435 (1979).ADSCrossRefGoogle Scholar
  5. 5.
    C. K. Biebricher, Darwinian selection of self-replicating RNA, in: Evolutionary Biology, M. K. Hecht, B. Wallace and G. T. Prance, eds., Vol. 16, Plenum Press, New York (1982).Google Scholar
  6. 6.
    C. Dobkin, D. R. Mills, F. R. Kramer, and S. Spiegelman, RNA replication: Required intermediates and the dissociation of template, product, and Qβ replicase, Biochemistry 18: 2038 (1979).CrossRefGoogle Scholar
  7. 7.
    C. K. Biebricher, M. Eigen and R. Luce, Product analysis of RNA generated de novo by replicase, J. Mol. Biol. 148: 369 (1981).CrossRefGoogle Scholar
  8. 8.
    C. K. Biebricher, M. Eigen and R. Luce, Kinetic analysis of template-instructed and de novo RNA synthesis by replicase, J. Mol. Biol. 148: 391 (1981).CrossRefGoogle Scholar
  9. 9.
    C. K. Biebricher, S. Diekmann and R. Luce, Structural analysis of self-replicating RNA synthesized by replicase, J. Mol. Biol. 154: 629 (1982).CrossRefGoogle Scholar
  10. 10.
    C. K. Biebricher, Darwinian evolution of self-replicating RNA, Chemica scripta 26B: 51 (1986).Google Scholar
  11. 11.
    C. K. Biebricher and M. Eigen, Kinetics of RNA replication by replicase, in RNA Genetics, Vol. I: RNA-directed Virus Replication, E. Domingo, P. Ahlquist and J. J. Holland, eds., CRC Press, Boca Raton, FL (1987).Google Scholar
  12. 12.
    C. K. Biebricher, M. Eigen and W. C. Gardiner, Kinetics of RNA replication: Plus-minus asymmetry and double-strand formation, Biochemistry 23: 3186 (1984).CrossRefGoogle Scholar
  13. 13.
    C. K. Biebricher, M. Eigen and W. C. Gardiner, Kinetics of RNA replication: Competition and selection among self-replicating RNA species, Biochemistry 24: 6550 (1985).CrossRefGoogle Scholar
  14. 14.
    C. K. Biebricher, M. Eigen and W. C. Gardiner, Kinetics of RNA replication, Biochemistry 22: 2544 (1983).CrossRefGoogle Scholar
  15. 15.
    H. Otten, Ein Beitrag zur Durchführung von kontrollierten Evolutionsexperimenten mit biologischen Makromolekülen, Dissertation, Technical University Braunschweig (1988).Google Scholar
  16. 16.
    J. Maynard Smith, Evolutionary Genetics, Oxford University Press, Oxford (1989).Google Scholar
  17. 17.
    M. Eigen and P. Schuster, The hypercycle—a principle of natural self-organization, Part A: Emergence of the hypercycle, Naturwissenschaften 64: 541 (1977).ADSCrossRefGoogle Scholar
  18. 18.
    M. Eigen, The physics of evolution, Chemica scripta 26B: 13 (1986).Google Scholar
  19. 19.
    P. Schuster, The physical basis of molecular evolution, Chemica scripta 26B: 27 (1986).Google Scholar
  20. 20.
    D. E. Dykhuizen and D. L. Hartl, Selection in Chemostats, Microbiol. Rev. 47: 150 (1983).Google Scholar
  21. 21.
    F. R. Kramer, D. R. Mills, P. E. Cole, T. Nishihara and S. Spiegelman, Evolution in vitro, Sequence and phenotype of a mutant RNA resistant to ethidium bromide, J. Mol Biol. 89: 719 (1974).CrossRefGoogle Scholar
  22. 22.
    S. E. Luria and M. Delbrueck, Mutations of bacteria from virus sensitivity to virus resistance, Genetics 28: 491 (1943).Google Scholar
  23. 23.
    J. Lederberg and M. Zinder, Concentration of biochemical mutants of bacteria with penicillin, J. Am. Chem. Soc. 70: 4267 (1948).CrossRefGoogle Scholar
  24. 24.
    D. E. Lea, and C. A. Coulson, The distribution of the number of mutants in bacterial populations, J. Genet. 49: 264 (1949).CrossRefGoogle Scholar
  25. 25.
    A. Ncvick and L. Szilard, Experiments with the chemostat on spontaneous mutations of bacteria, Proc. Nat. Acad. Sci. USA 34: 708 (1950).ADSCrossRefGoogle Scholar
  26. 26.
    H. Moser, Structure and dynamics of bacterial populations maintained in the chemostat, Cold Spring Harbor Symp. Quant. Biol. 22: 121 (1957).CrossRefGoogle Scholar
  27. 27.
    R. Levisohn and S. Spiegelman, The cloning of a self-replicating RNA molecule, Proc. Nat. Acad. Sci. USA 60: 866 (1968).ADSCrossRefGoogle Scholar
  28. 28.
    C. K. Biebricher, Replication and evolution of short-chained RNA species replicated by replicase, Cold Spring Harb. Symp. Quant. Biol. 52: 299 (1987).CrossRefGoogle Scholar
  29. 29.
    M. Eigen and C. K. Biebricher, Sequence space and quasispecies distribution, in RNA Genetics, Vol. III: Variability of RNA Genomes, E. Domingo, P. Ahlquist and J. J. Holland, eds., CRC Press, Boca Raton FL (1987).Google Scholar
  30. 30.
    N. Hilliger, Bestimmung der Selektionswerte der Mutanten einer Quasis-peziesverteilung, Masters thesis, Göttingen University (1990).Google Scholar
  31. 31.
    Batschelet, E. Domingo and C. Weissmann, The proportion of revertant and mutant phage in a growing population, as a function of mutation and growth rate, Gene 1: 27 (1976).CrossRefGoogle Scholar
  32. 32.
    E. Domingo, D. Sabo, T. Taniguchi and C. Weissmann, Nucleotide sequence heterogeneity of an RNA phage population, Cell 13: 735 (1978).CrossRefGoogle Scholar
  33. 33.
    A. R. Fersht, Fidelity of replication of phage φX174 by DNA polymerase III holoen-zyme: Spontaneous mutation by misincorporation, Proc. Natl. Acad. Sci. USA 76: 4946 (1979).ADSCrossRefGoogle Scholar
  34. 34.
    L. A. Loeb and T. A. Kunkel, Fidelity of DNA synthesis, Annu. Rev. Biochem. 52: 429 (1982).CrossRefGoogle Scholar
  35. 35.
    J. S. McCaskill, A localization threshold for macromolecular quasispecies from continuously distributed replication rates, J. Chem. Phys. 80(10): 5194 (1984).MathSciNetADSCrossRefGoogle Scholar
  36. 36.
    C. L. Thompson and J. L. McBride, On Eigen’s theory of the self-organization of matter and the evolution of biological macromolecules, Math. Biosci. 21: 127 (1974).MathSciNetMATHCrossRefGoogle Scholar
  37. 37.
    S. J. Gould and N. Eldredge, Punctuated equilibria: the tempo and mode of evolution reconsidered, Paleobiology 3: 115–151 (1977).Google Scholar
  38. 38.
    L. Demetrius, Growth rate, population entropy, and perturbation theory, Math. Biosc. 93: 159 (1989).MathSciNetMATHCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Christof K. Biebricher
    • 1
  • M. Eigen
    • 1
  • William C. GardinerJr.
    • 2
  1. 1.Max-Planck-Institut für Biophysikalische ChemieGöttingenGermany
  2. 2.Department of ChemistryUniversity of TexasAustinUSA

Personalised recommendations