Molecular and General Genetics MGG

, Volume 251, Issue 5, pp 503–508 | Cite as

Gene conversion as a focusing mechanism for correlated mutations: a hypothesis

  • J. Ninio
Original Paper


Ways of producing complex mutational events without substantially raising the primary mutation rate are explored. If the small amount of DNA that is resynthesised through the action of the mismatch DNA repair system is not subject to further repair, the incidence of double mutations can increase by a factor of 100, while single mutations would increase by only 30%. Such a boost in the incidence of double mutations seems insufficient to meet the needs of higher organisms. For them, an alternative strategy would be to produce complex events by a succession of single mutations occurring in a correlated manner over several sexual generations. It is proposed that gene conversion may fulfill this role. Assuming that the resynthesis of DNA that occurs during gene conversion produces mutations in the conversion tract, one predicts a tendency for close mutations in corresponding sequences in the two homologous chromosomes, to promote, during conversion, further mutations in their vicinity. Semiquantitative calculations suggest that such a mechanism can be quite effective, provided the divergence between two paired chromosomes is around 10−4 or less. Such a mechanism might constitute an adaptive mutation strategy acting at the population level.

Key words

Mutation strategies Mutation rates DNA mismatch repair Gene conversion Polymorphism 


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  1. Aquadro CF (1992) Why is the genome variable? Insights fromDrosophila. Trends Genet 8:355–362Google Scholar
  2. Bebenek K, Roberts JD, Kunkel TA (1992) The effects of dNTP pool imbalances on frameshift fidelity during DNA replication. J Biol Chem 267:3589–3596Google Scholar
  3. Drake JW (1991) A constant rate of spontaneous mutation in DNA-based microbes. Proc Nat Acad Sci USA 88:7160–7164Google Scholar
  4. Dover G (1982) Molecular drive: a cohesive mode of species evolution. Nature 299:111–117Google Scholar
  5. Gillespie JH (1991) The causes of molecular evolution. Oxford University Press, Oxford-New YorkGoogle Scholar
  6. Glickman BW, Ripley LS (1984) Structural intermediates of deletion mutagenesis: a role for palindromic DNA. Proc Nat Acad Sci USA 81: 512–516Google Scholar
  7. Gutell RR, Weiser B, Woese CR, Noller HF (1985) Comparative anatomy of 16S-like ribosomal RNA. Prog Nucleic Acids Res Mol Biol 32:155–216Google Scholar
  8. Hilliker AJ, Chovnick A (1981) Further observations on intragenic recombination inDrosophila melanogaster. Genet Res 38:281–296Google Scholar
  9. Hilliker AJ, Harauz G, Reaume AG, Gray M, Clark SH, Chovnick A (1994) Meiotic gene conversion tract length distribution within therosy locus ofDrosophila melanogaster. Genetics 137:1019–1026Google Scholar
  10. Holliday R (1964) A mechanism for gene conversion in fungi. Genet Res 5:282–304Google Scholar
  11. Jin DJ, Gross GA (1988) Mapping and sequencing of mutations in theEscherichia coli rpoB gene that lead to rifampicin resistance. J Mol Biol 202:45–58Google Scholar
  12. Kricker MC, Drake JW, Radman M (1992) Duplication-targeted DNA methylation and mutagenesis in the evolution of eukaryotic chromosomes. Proc Nat Acad Sci USA 89:1075–1079Google Scholar
  13. Lecomte PJ, Ninio J (1987) Variations with position of replication errors due to exonuclease warm-up. FEBS Lett 221:194–198Google Scholar
  14. Li W-H, Sadler LA (1991) Low nucleotide diversity in man. Genetics 129:513–523Google Scholar
  15. Matic I, Rayssiguier C, Radman M (1995) Interspecies gene exchange in bacteria: the role of SOS and mismatch repair systems in evolution of species. Cell 80:507–515Google Scholar
  16. Nei M (1987) Molecular evolutionary genetics. Columbia University Press, New YorkGoogle Scholar
  17. Ninio J (1991a) Transient mutators: a semiquantitative analysis of the influence of translation and transcription errors on mutation rates. Genetics 129:957–962Google Scholar
  18. Ninio J (1991b) Connections between translation, transcription and replication error-rates. Biochimie 73:1517–1523Google Scholar
  19. Pathak VK, Temin HR (1990) Broad spectrum ofin vivo forward mutations, hypermutations, and mutational hotspots in a retroviral shuttle vector after a single replication cycle: substitutions, frameshifts, and hypermutations. Proc Nat Acad Sci USA 87:6019–6023Google Scholar
  20. Radman M, Wagner R (1993) Mismatch recognition in chromosomal interactions and speciation. Chromosoma 102:369–373Google Scholar
  21. Ripley LS (1991) Concerted mutagenesis: its potential impact on interpretation of evolutionary relationships. In: Klein J, Klein D (eds) Molecular Evolution of the Major Histocompatibility Complex. NATO ASI Series, vol H59. Springer-Verlag, Berlin, pp 63–94Google Scholar
  22. Rhounim L, Rossignol J-L, Faugeron G (1992) Epimutation of repeated genes inAscobolus immersus. EMBO J 11:4451–4457Google Scholar
  23. Schaaper RM, Dunn RL (1991) Spontaneous mutation in theEscherichia coli lacI gene. Genetics 129:317–326Google Scholar
  24. Schaeffer SW, Miller EL (1993) Estimates of linkage disequilibrium and the recombination parameter determined from segregating nucleotide sites in the alcohol dehydrogenase region ofDrosophila pseudoobscura. Genetics 135:541–552Google Scholar
  25. Selker EU (1990) Premeiotic instability of repeated sequences inNeurospora crassa. Annu Rev Genet 24:579–613Google Scholar
  26. Timms AR, Bridges BA (1993) Double, independent mutational events in therpsL gene ofEscherichia coli: an example of hypermutability? Mol Microbiol 9:335–342Google Scholar
  27. West SW (1992) Enzymes and molecular mechanisms of genetic recombination. Annu Rev Biochem 61:603–640Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • J. Ninio
    • 1
  1. 1.Laboratoire de Physique Statistique, Ecole Normale SupérieureParis Cedex 05France

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