Hostname: page-component-586b7cd67f-2brh9 Total loading time: 0 Render date: 2024-11-26T08:47:33.675Z Has data issue: false hasContentIssue false
  • English
  • Français

The role of DNA replication and isochores in generating mutation and silent substitution rate variance in mammals

Published online by Cambridge University Press:  14 April 2009

Adam Eyre Walker
Adam Eyre Walker
Affiliation:
Institute of Cell Animal and Population Biology, University of Edinburgh, Edinburgh, EH9 3JT, Great Britain
Rights & Permissions [Opens in a new window]

Summary

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

It has been suggested that isochores are maintained by mutation biases, and that this leads to variation in the rate of mutation across the genome. A model of DNA replication is presented in which the probabilities of misincorporation and proofreading are affected by the composition and concentration of the free nucleotide pools. The relationship between sequence G + C content and the mutation rate is investigated. It is found that there is very little variation in the mutation rate between sequences of different G + C contents if the total concentration of the free nucleotides remains constant. However, variation in the mutation rate can be arbitrarily large if some mismatches are proofread and the total concentration of free nucleotides varies. Hence the model suggests that the maintenance of isochores by the replication of DNA in free nucleotide pools of biased composition does not lead per se to mutation rate variance. However, it is possible that changes in composition could be accompanied by changes in concentration, thus generating mutation rate variance. Furthermore, there is the possibility that germ-line selection could lead to alterations in the overall free nucleotide concentration through the cell cycle. These findings are discussed with reference to the variance in mammalian silent substitution rates.

Type
Research Article
Information
Genetics Research , Volume 60 , Issue 1 , August 1992 , pp. 61 - 67
Copyright
Copyright © Cambridge University Press 1992

References

Aissani, B.D'Onofrio, G.Mouchiroud, D.Gardiner, K. & Bernardi, G. (1991). The compositional properties of human genes. Journal of Molecular Evolution 32,493–503.CrossRefGoogle ScholarPubMed
Bernardi, G. (1989). The isochore organization of the human genome. Annual Review of Genetics 23, 637–661.CrossRefGoogle ScholarPubMed
Bernardi, G.Olofsson, B.Filipski, J.Zerial, M.Salinas, J.Cuny, G.Meunier-Rotival, M. & Rodier, F. (1985). The mosaic genome of warm blooded vertebrates. Science 228, 953–958.CrossRefGoogle ScholarPubMed
Bohr, V. A.Phillips, D. H. & Hanawalt, P. C. (1987). Heterogeneous DNA damage and repair in the mammalian genome. Cancer Research 47, 6426–6436.Google ScholarPubMed
Brown, T. C. & Jiricny, J. (1988). Different base/base mispairs are corrected with different efficiencies and specificities in monkey kidney cells. Cell 54, 705–711.CrossRefGoogle ScholarPubMed
Brown, T. C. & Jiricny, J. (1989). Repair of base-base mismatches in simian and human cells. Genome 31, 578–583.CrossRefGoogle ScholarPubMed
Bulmer, M.Wolfe, K. H. & Sharp, P. M. (1991). Synonymous nucleotide substitution rates in mammalian genes: implications for the molecular clock and the relationships of the mammalian orders. Proceedings of the National Academy of Science USA 88, 5974–5978.CrossRefGoogle ScholarPubMed
Eyre-Walker, A. (1991). An analysis of codon usage in mammals: selection or mutation bias. Journal of Molecular Evolution 33, 442–449.Google Scholar
Filipski, J. (1988). Why the rate of silent substitution is variable within the a vertebrate's genome. Journal of Theoretical Biology 134, 159–164.CrossRefGoogle ScholarPubMed
Gojobori, T.Li, W.-H & Graur, D. (1982). Patterns of mutation in pseudogenes and functional genes. Journal of Molecular Biology 18, 360–369.Google Scholar
Goldman, M. A. (1988). The chromatin domain as a unit of gene regulation. Bioessays 9, 50–55.Google Scholar
Hastings, I. M. (1989). Potential germline competition in animals and its evolutionary implications. Genetics 123, 191–197.CrossRefGoogle ScholarPubMed
Holmquist, G. P. (1987). Role of replication time in the control of tissue specific gene expression. American Journal of Human Genetics 40, 151–173.Google ScholarPubMed
Holmquist, G. P. (1989). Evolution of chromosome bands: molecular ecology of non-coding DNA. Journal of Molecular Evolution 28, 469–486.CrossRefGoogle Scholar
Ikemura, T. & Aota, S. (1988). Global variation in G + C content along vertebrate genome DNA: possible correlation with chromosome band structures. Journal of Molecular Biology 203, 1–13.Google Scholar
Kohalmi, S. E.Glattke, M.McIntosh, E. M. & Kunz, B. A. (1991). Mutational specificity of DNA precursor pool imbalances in yeast arising from deoxycytidylate deaminase deficiency or treatment with thymidylate. Journal of Molecular Biology 220, 933–946.CrossRefGoogle ScholarPubMed
Kunkel, T. A.Sabatino, R. D. & Bambara, R. A. (1987). Exonucleolytic proofreading by calf thymus DNA polymerase delta. Proceedings of National Academy Science USA 84, 4865–4869.Google Scholar
Leeds, J. M.Slabaugh, M. B.Mathews, C. K. (1985). DNA precursor pools and ribonucleotide reductase activity: distribution between the nucleus and the cytoplasm of mammalian cells. Molecular and Cellular Biology 5, 3443–3450.Google ScholarPubMed
Li, W.-H.Wu, C.-I & Luo, C.-C. (1984). Nonrandomness of point mutation as reflected in nucleotide substitutions in pseudogenes and its evolutionary implications. Journal of Molecular Evolution 21, 58–71.Google Scholar
Li, W.-H.Tanimura, M. & Sharp, P. M. (1987). An evaluation of the molecular clock hypothesis using mammalian DNA sequences. Journal of Molecular Evolution 25, 330–342.Google Scholar
Matthews, C. K. & Slabaugh, M. B. (1986). Eukaryotic DNA metabolism: are deoxyribonucleotides channelled to replication sites? Experimental Cell Research 162, 285–295.Google Scholar
McCormick, P. J.Danhauser, L. L.Rustim, Y. M. & Bertram, J. S. (1983). Changes in ribo-and deoxyribonucleoside triphosphate pools within the cell cycle of a synchronised mouse fibroblast cell line. Biochima Biophysica Ada 755, 36–40.Google Scholar
Meuth, M. (1989). The molecular basis of mutations induced by deoxyribonucleoside triphosphate pool imbalances in mammalian cells. Experimental Cell Research 181, 305–316.CrossRefGoogle ScholarPubMed
Phear, G. & Meuth, M. (1989 a). A novel pathway for transversion mutation induced by dCTP misincorporation in a mutator strain of CHO cells. Molecular and Cellular Biology 9, 1810–1812.Google Scholar
Phear, G. & Meuth, M. (1989 b). The genetic consequences of DNA precursor pool imbalance: sequence analysis of mutations induced by excess thymidine at the hamster aprt locus. Mutation Research 214, 201–206.CrossRefGoogle ScholarPubMed
Sharp, P. M. (1989). Evolution at ‘Silent’ sites in DNA. In Evolution and Animal Breeding: Reviews on Molecular and Quantitative Approaches in Honour of Alan Robertson. (ed. Hill, W. G.Mackay, T. F. C.). Wallingford CAB International 1989, pp. 23–31.Google Scholar
Ticher, A. & Grauer, D. (1989). Nucleic acid composition, codon usage, and the rate of synonymous substitution in protein coding genes. Journal of Molecular Evolution 28, 286–298.CrossRefGoogle ScholarPubMed
Wolfe, K. (1991). Mammalian DNA replication: mutation biases and the mutation rate. Journal of Theoretical Biology 149, 441–451.Google Scholar
Wolfe, K.Sharp, P. M. & Li, W.-H. (1989). Mutation rates differ among regions of the mammalian genome. Nature 337, 283–285.CrossRefGoogle ScholarPubMed