Skip to main content
Log in

Directional mutation pressure, mutator mutations, and dynamics of molecular evolution

  • Published:
Journal of Molecular Evolution Aims and scope Submit manuscript

Abstract

Using a general form of the directional mutation theory, this paper analyzes the effect of mutations in mutator genes on the G + C content of DNA, the frequency of substitution mutations, and evolutionary changes (cumulative mutations) under various degrees of selective constraints. Directional mutation theory predicts that when the mutational bias between A/T and G/C nucleotide pairs is equilibrated with the base composition of a neutral set of DNA nucleotides, the mutation frequency per gene will be much lower than the frequency immediately after the mutator mutation takes place. This prediction explains the wide variation of the DNA G + C content among unicellular organisms and possibly also the wide intragenomic heterogeneity of third codon positions for the genes of multicellular eukaryotes. The present analyses lead to several predictions that are not consistent with a number of the frequently held assumptions in the field of molecular evolution, including belief in a constant rate of evolution, symmetric branching of phylogenetic trees, the generality of higher mutation frequency for neutral sets of nucleotides, the notion that mutator mutations are generally deleterious because of their high mutation rates, and teleological explanations of DNA base composition.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Atwood KC, Schneider LK, Ryan FJ (1951) Selective mechanisms in bacteria. Cold Spring Harbor Symp Quant Biol 16:345–354

    PubMed  CAS  Google Scholar 

  • Belozersky AN, Spirin AS (1958) A correlation between the compositions of deoxyribonucleic and ribonucleic acids. Nature 182:111–112

    PubMed  CAS  Google Scholar 

  • Bernardi G, Olfsson B, Filipski J, Zerial M, Salinas J, Cuny G, Meunier-Rotival M, Rodier F (1985) The mosaic genome of the vertebrates. Science 228:953–958

    PubMed  CAS  Google Scholar 

  • Bernardi G, Bernardi G (1985) Codon usage and genome composition. J Mol Evol 22:363–365

    Article  PubMed  CAS  Google Scholar 

  • Bernardi, G., Mouchiroud D, Gautier C, Bernardi G (1988) Compositional patterns in vertebrate genomes: Conservation and change in evolution. J Mol Evol 28:7–18

    Article  PubMed  CAS  Google Scholar 

  • Bernardi G, Bernardi G (1991) Compositional properties of nuclear genes from cold-blooded vertebrates. J Mol Evol 33:57–67

    Article  CAS  Google Scholar 

  • Bohr VA, Phillips DH, Hanawalt PC (1987) Heterogeneous DNA damage and repair in the mammalian genome. Cancer Res 47:6426–6436

    PubMed  CAS  Google Scholar 

  • Chao L, Cox EC (1983) Competition between high and low mutating strains ofEscherichia coli. Evolution 37:125–134

    Article  Google Scholar 

  • Chargaff E (1955) Isolation and composition of the deoxypentose nucleic acids and of the corresponding nucleoproteins. In: Chargaff E, Davidson JN, (eds)The nucleic acids, vol. 1, Academic Press, New York

    Google Scholar 

  • Cheng KC, Cahill DS, Kasai H, Nishimura S, Loeb LA (1992) 8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G → T and A → C substitutions. J Biol Chem 267:166–172

    PubMed  CAS  Google Scholar 

  • Cox EC, Yanofsky C (1967) Altered base ratios in the DNA of anEscherichia coli mutator strain. Proc Natl Acad Sci USA 58:1895–1902

    PubMed  CAS  Google Scholar 

  • Cox EC, Yanofsky C (1969) Mutator gene studies inEscherichia coli. J Bacterial 100:390–397

    CAS  Google Scholar 

  • Cox EC (1973) Mutator gene studies inEscherichia coli: ThemutT gene. Genetics (Suppl) 73:67–80

    CAS  Google Scholar 

  • Cox EC, Gibson TC (1974) Selection for high mutation rates in chemostats. Genetics 77:169–184

    PubMed  CAS  Google Scholar 

  • Cox EC (1976) Bacterial mutator genes and the control of spontaneous mutation. Ann Rev Genet 10:135–156

    Article  PubMed  CAS  Google Scholar 

  • Drake JW (1966) Spontaneous mutations accumulating in bacteriophage T4 in the complete absence of DNA replication. Proc Natl Acad Sci USA 55:738–743

    PubMed  CAS  Google Scholar 

  • Felsenstein J (1981) Evolutionary trees from DNA sequences: A maximum likelihood approach. J Mol Evol 17:368–376

    Article  PubMed  CAS  Google Scholar 

  • Felsenstein J (1982) Numerical method for inferring evolutionary trees. Q Rev Biol 57:379–404

    Article  Google Scholar 

  • Filipski J (1987) Correlation between molecular clock ticking, codon usage, fidelity of DNA repair, chromosome banding and chromatin compactness in the germline cells. FEBS Lett 217:184–186

    Article  PubMed  CAS  Google Scholar 

  • Filipski J (1990) Evolution of DNA sequence: Contributions of mutational bias and selection to the origin of chromosomal compartments. Adv Mutagen Res 2:1–54

    Google Scholar 

  • Fitch WM, Margoliash E (1967) Construction of phylogenetic trees. Science 155:279–284

    PubMed  CAS  Google Scholar 

  • Fowler RG, Degnen GE, Cox EC (1974) Mutational specificity of a conditionalEscherichia coli mutator,mutD5. Mol Gen Genet 133:179–191

    Article  PubMed  CAS  Google Scholar 

  • Freese E (1962) On the evolution of base composition of DNA. J Theor Biol 3:82–101

    CAS  Google Scholar 

  • Gibson TC, Scheppe ML, Cox EC (1974) Fitness of anEscherichia coli mutator gene. Science 169:686–88

    Google Scholar 

  • Hastings KEM, Emerson CP (1983) Codon usage in muscle genes and liver genes. J Mol Evol 19:214–218

    Article  PubMed  CAS  Google Scholar 

  • Ikemura T (1981) Correlation between the abundance of Escherichia coli transfer RNAs and the occurrence of the respective codons in its protein genes. J Mol Biol 146:1–21

    Article  PubMed  CAS  Google Scholar 

  • Ikemura T (1985) Codon usage and t-RNA content in unicellular and multicellular organisms. Mol Biol Evol 2:13–34

    PubMed  CAS  Google Scholar 

  • Jukes TH, Bhushan V (1986) Silent nucleotide substitutions and G + C content of some mitochondrial and bacterial genes. J Mol Evol 24:39–44

    Article  PubMed  CAS  Google Scholar 

  • Kano A, Andai Y, Ohama T, Osawa S (1991) Novel anticodon composition of transfer RNAs inMicrococcus luteus, a bacterium with a high genomic G + C content: correlation with codon usage. J Mol Evol 221:387–401

    CAS  Google Scholar 

  • Kasai H, Nishimura S (1986) Hydroxylation of guanine in nucleosides and DNA at the C-8 position by heated glucose and oxygen radical-forming agents. Environ Health Perspectives 67:111–116

    CAS  Google Scholar 

  • Kimura M (1967) On the evolutionary adjustment of spontaneous mutation rates. Genet Res 9:25–34

    Article  Google Scholar 

  • Kimura M (1983)The neutral theory of molecular evolution. Cambridge University Press, Cambridge

    Google Scholar 

  • Kimura M, Ohta T (1969) The average number of generations until fixation of a mutant gene in a finite population. Genetics 61:763–771

    PubMed  Google Scholar 

  • King JL, Jukes TH (1969) Non-Darwinian evolution. Science 164:788–798

    PubMed  CAS  Google Scholar 

  • Langley CH, Fitch WM (1974) An examination of the constancy of the rate of molecular evolution. J Mol Evol 3:161–177

    Article  PubMed  CAS  Google Scholar 

  • Lawrence JG, Hartl DL, Ochman H (1991) Molecular considerations in the evolution of bacterial genes. J Mol Evol 33:241–250

    Article  PubMed  CAS  Google Scholar 

  • Lee KY, Wahl R, Barbu E (1956) Contenu en bases puriques et pyrimidiques des acids désoxyribonucléiques des bactéries. Ann Inst Pasteur 91:212–224

    CAS  Google Scholar 

  • Leigh EG (1970) Natural selection and mutability. Am Naturalist 104:301–305

    Article  Google Scholar 

  • Li WH, Wu CI, Luo CC (1985) A new method for estimating synonymous and nonsynonymous rates of nucleotide substitution considering the relative likelihood of nucleotide and codon changes. Mol Biol Evol 2:150–174

    PubMed  Google Scholar 

  • MacHattie LA, Thomas CA (1970) Viral DNA molecules. In: Sober HA, Harte RA, Sober EK (eds) Handbook of biochemistry, selected data for molecular biology, 2nd ed. pp H3-H16, The Chemical Rubber Co., Cleveland, Ohio

    Google Scholar 

  • Maki H, Sekiguchi M (1992)MutT protein specifically hydrolyses a potent mutagenic substrate for DNA synthesis. Nature 355:273–275

    Article  PubMed  CAS  Google Scholar 

  • Muto A, Osawa S (1987) The guanine and cytosine content of genomic DNA and bacterial evolution. Proc Natl Acad Sci USA 84:166–169

    PubMed  CAS  Google Scholar 

  • Muto A, Andachi Y, Yuzawa H, Yamao Y, Osawa S (1990) The organization and evolution of transfer RNA genes inMycoplasma capricolum. Nucleic Acids Res 18:5037–5043

    PubMed  CAS  Google Scholar 

  • Nestmann ER, Hill RF (1973) Population changes in continuously growing mutator cultures ofEscherichia coli. Genetics (Suppl) 73:41–44

    Google Scholar 

  • Nomura M, Sor F, Yamagishi M, Lawson M (1987) Heterogeneity of GC content within a single bacterial genome and its implication for evolution. Cold Spring Harbor Symp Quant Biol 52:658–663

    Google Scholar 

  • Normore WM, Brown JR (1970) Guanine plus cytosine (G + C) composition of bacteria. In: Sober HA, Harte RA, Sober EK (eds) Handbook of biochemistry, selected data for molecular biology, 2nd ed. pp H24-H74, The Chemical Rubber Co., Cleveland, Ohio

    Google Scholar 

  • Ogasawara N (1985) Markedly unbiased codon usage inBacillus subtilis. Gene 40:145–150

    Article  PubMed  CAS  Google Scholar 

  • Ohama T, Muto A, Osawa S (1990) Role of GC-biased mutation pressure on synonymous codon choice inMicrococcus luteus, a bacterium with a high genomic GC-content. Nucleic Acids Res 18:1565–1569

    PubMed  CAS  Google Scholar 

  • Ohno S (1988) Universal rule for coding sequence constriction: AT/CG deficiency-TG/CT excess. Proc Natl Acad Sci USA 85:9630–9634

    PubMed  CAS  Google Scholar 

  • Osawa S, Ohama T, Yamao F, Muto A, Jukes TH, Ozeki H, Umesono K (1988) Directional mutation pressure and transfer RNA in choice of the third nucleotide of synonymous two codon sets. Proc Natl Acad Sci USA 85:1124–1128

    PubMed  CAS  Google Scholar 

  • Painter PR (1975) Mutator genes and selection for the mutation rate in bacteria. Genetics 79:649–660

    PubMed  CAS  Google Scholar 

  • Rolfe R, Messelson M (1959) The relative homogeneity of microbial DNA. Proc Natl Acad Sci USA 45:1039–1043

    PubMed  CAS  Google Scholar 

  • Shapiro HS (1970) Distribution of purines and pyrimidines deoxyribonucleic acids. In: Sober HA, Harte RA, Sober EK (eds) Handbook of biochemistry, selected data for molecular biology, 2nd ed. pp H80-H98, The Chemical Rubber Co., Cleveland, Ohio

    Google Scholar 

  • Sharp PM, Li WH (1986) An evolutionary perspective on synonymous codon usage in unicellular organisms. J Mol Evol 24:28–38

    Article  PubMed  CAS  Google Scholar 

  • Sharp PM, Cowe E, Higgins DG, Shields DC, Wolfe KH, Wright F (1988) Codon usage patterns inEscherichia coli, Bacillus subtilis, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Drosophila melanogaster and Homo sapiens; a review of the considerable within-species diversity. Nucleic Acids Res. 16:8207–8211

    PubMed  CAS  Google Scholar 

  • Sharp PM, Li WH (1986) Codon usage in regulatory genes inEscherichia coli does not reflect selection for ‘rare’ codons. Nucleic Acids Res 14:7737–7749

    PubMed  CAS  Google Scholar 

  • Shields DC, Sharp PM (1987) Synonymous codon usage inBacillus subtilis reflects both translational selection and mutational biases. Nucleic Acids Res 15:8023–8040

    PubMed  CAS  Google Scholar 

  • Shields DC, Sharp PM, Higgins DG, Wright F (1988) “Silent” site inDrosophila genes are not neutral: Evidence of selection among synonymous codons. Mol Biol Evol 5:704–716

    PubMed  CAS  Google Scholar 

  • Shields DC (1990) Switches in species-specific codon preferences: the influence of mutation biases. J Mol Evol 31:71–80

    Article  PubMed  CAS  Google Scholar 

  • Sueoka N (1962) On the genetic basis of variation and heterogeneity of DNA base composition. Proc Natl Acad Sci USA 48:582–592

    PubMed  CAS  Google Scholar 

  • Sueoka N (1988) Directional mutation pressure and neutral molecular evolution. Proc Natl Acad Sci USA 85:2653–2657

    PubMed  CAS  Google Scholar 

  • Sueoka N (1992) Directional mutation pressure and molecular evolution: equilibria and asymmetric phylogenetic branching. J Mol Evol 34:95–114

    Article  PubMed  CAS  Google Scholar 

  • Sueoka N, Marmur J, Doty P (1959) Heterogeneity in deoxyribonucleic acids. II. Dependence of the density of deoxyribonucleic acids on guanine-cytosine. Nature 183:1427–1431

    Google Scholar 

  • Treffers HP, Spinelli V, Belser NO (1954) A factor (or mutator gene) influencing mutation rates inEscherichia coli. Proc Natl Acad Sci USA 40:064–1071

    Google Scholar 

  • Wada A, Suyama A (1986) Local stability of DNA and RNA secondary structure and its relation to biological functions. Prog Biophys Mol Biol 47:113–157

    Article  PubMed  CAS  Google Scholar 

  • Wilson AC, Carlson SS, White RJ (1977) Biochemical evolution. Ann Rev Biochem 46:573–639

    Article  PubMed  CAS  Google Scholar 

  • Wolfe KH, Sharp PM, Li WH (1989) Mutation rates differ among regions of the mammalian genome. Nature 337:283–285.

    Article  PubMed  CAS  Google Scholar 

  • Wright S (1931) Evolution in Mendelian populations. Genetics 16:97–159

    PubMed  CAS  Google Scholar 

  • Yanofsky C, Cox EC, Horn V (1966) The unusual mutagenic specificity of anE. coli mutator gene. Proc Natl Acad Sci USA 55:274–281

    PubMed  CAS  Google Scholar 

  • Yomo T, Ohno S (1989) Concordant evolution of coding and noncoding regions of DNA made possible by the universal rule of AT/CG deficiency-TG/CT excess. Proc Natl Acad Sci USA 86:8452–8456

    PubMed  CAS  Google Scholar 

  • Zuckerkandl E, Pauling L (1965) Evolutionary divergence and convergence in proteins. In: Bryson V, Vogel HJ (eds) Evolving genes and proteins. Academic Press, New York, pp 97–166

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sueoka, N. Directional mutation pressure, mutator mutations, and dynamics of molecular evolution. J Mol Evol 37, 137–153 (1993). https://doi.org/10.1007/BF02407349

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02407349

Key words

Navigation