Skip to main content
SpringerLink
Log in

The molecular clock revisited: the rate of synonymous vs. replacement change in Drosophila

  • Published:
Genetica Aims and scope Submit manuscript

Abstract

Rates of synonymous and nonsynonymous substitution were investigated for 24 genes in three Drosophila species, D. pseudoobscura, D. subobscura, and D. melanogaster. D. pseudoobscura and D. subobscura, two distantly related members of the obscura clade, differ on average by 0.29 synonymous nucleotide substitutions per site. D. melanogaster differs from the two obscura species by an average of 0.81 synonymous substitutions per site. Using a method developed by Gillespie, we investigated the variance to mean ratio, or Index of Dispersion, R, of substitutions along the three species' branches to test the fundamental prediction of the neutral theory of molecular evolution, E(R) = 1. For nonsynonymous substitutions, the average R, Ra is 1.6, which is not significantly different from the neutral theory prediction. Only 5 of the 24 genes had significantly large Ra valves, and 12 of the genes had Ra estimates of less than one. In contrast, the Index of Dispersion for synonymous substitutions was significantly large for 12 of the 24 genes, with an average of Rs = 4.4, also statistically significant. These findings contrast with results for mammals, which showed overdispersion of nonsynonymous substitutions, but not of synonymous substitutions. Weak selection acting to maintain codon bias in Drosophila, but not in mammals, may be important in explaining the high variance in the rate of synonymous substitutions in this group of organisms.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Akashi, H., 1994. Synonymous codon usage in Drosophila melanogaster: Natural selection and translational accuracy. Genetics 136: 927-935.

    PubMed  CAS  Google Scholar 

  • Akashi, H., 1995. Inferring weak selection from patterns of polymorphism and divergence at ‘silent’ sites in Drosophila DNA. Genetics 139: 1067-1076.

    PubMed  CAS  Google Scholar 

  • Benson, A.R., 1995. The molecular evolution of the obscura group Chorion s15: A prominent role for codon bias. PhD thesis, Harvard University.

  • Britten, R.J., 1986. Rates of DNA sequence evolution differ between taxonomic groups. Science 231: 1393-1398.

    PubMed  CAS  Google Scholar 

  • Bulmer, M., 1989. Estimating the variability of substitution rates. Genetics 123: 615-619.

    PubMed  CAS  Google Scholar 

  • Bulmer, M., K.H. Wolfe, & P.M. Sharp, 1991. Synonymous nucleotide substitution rates in mammalian genes: implications for the molecular clock and the relationship ofmammalian orders. Proc. Natl. Acad. Sci. USA 88: 5974-5978.

    Article  PubMed  CAS  Google Scholar 

  • Chao, L. & D.E. Carr, 1993. The molecular clock and the relationship between population size and generation time. Evolution 47: 688-690.

    Article  Google Scholar 

  • Comeron, J.M., 1995. A method for estimating the numbers of synonymous and nonsynonymous substitutions per site. J. Mol. Evol. 41: 1152-1159.

    Article  PubMed  CAS  Google Scholar 

  • Comeron, J.M., 1997. Estudi de la variabilitat nucleotidica a Drosophila: RegiÛ Xdh a D. subobscura. PhD thesis. Barcelona, Spain. Universitat de Barcelona.

    Google Scholar 

  • Easteal, S., 1988. Rate constancy of globin gene evolution in placental mammals. Proc. Natl. Acad. Sci. 85: 7622-7626.

    Article  PubMed  CAS  Google Scholar 

  • Easteal, S., 1990. The pattern of mammalian evolution and the relative rate test of molecular evolution. Genetics 124: 165-173.

    PubMed  CAS  Google Scholar 

  • Easteal, S. & C. Collet, 1994. Consistent variation in amino-acid substitution rate, despite uniformity of mutation rate: Protein evolution in mammals is not neutral. Mol. Biol. Evol. 11: 643- 647.

    PubMed  CAS  Google Scholar 

  • Gillespie, J.H., 1984. The molecular clock may be an episodic clock. Proc. Natl. Acad. Sci. USA 81: 8009-8013.

    Article  PubMed  CAS  Google Scholar 

  • Gillespie, J.H., 1986a. Variability of evolutionary rates of DNA. Genetics 113: 1077-1091.

    PubMed  CAS  Google Scholar 

  • Gillespie, J.H., 1986b. Rates of molecular evolution. Annu. Rev. Ecol. Syst. 17: 637-665.

    Article  Google Scholar 

  • Gillespie, J.H., 1987. Molecular evolution and the neutral allele theory. Oxford Surveys Evol. Biol. 4: 10-37.

    Google Scholar 

  • Gillespie, J.H., 1989. Lineage effects and the index of dispersion of molecular evolution. Mol. Biol. Evol. 6: 636-647.

    PubMed  CAS  Google Scholar 

  • Gillespie, J.H., 1991. The Causes of Molecular Evolution. Oxford series in Ecology and evolution. Oxford University Press. New York.

    Google Scholar 

  • Gillespie, J.H., 1993. Substitution processes in molecular evolution. I. Uniform and clustered substitutions in haploid model. Genetics 134: 971-981.

    PubMed  CAS  Google Scholar 

  • Gillespie, J.H., 1994a. Substitution processes in molecular evolution. II. Exchangeable models from population genetics. Evolution 48: 1101-1113.

    Article  Google Scholar 

  • Gillespie, J.H., 1994b. Substitution processes in molecular evolution. III. Deleterious alleles. Genetics 138: 943-952.

    PubMed  CAS  Google Scholar 

  • Goddard, K., A. Caccone & J.R. Powell, 1990. Evolutionary implications of DNA divergence in the Drosophila obscura group. Evolution 44: 1656-1670.

    Article  Google Scholar 

  • Jukes, T. H., & C. R. Cantor, 1969. Evolution of protein molecules. pp. 21-132 in Mammalian Protein Metabolism III, edited by H. N. Munro. Academic Press, New York.

    Google Scholar 

  • Kimura, M., 1969. The rate of molecular evolution considered from the standpoint of population genetics. Proc. Natl. Acad. Sci. USA 63: 1181-1188.

    Article  PubMed  CAS  Google Scholar 

  • Kimura, M., 1983. The Neutral Theory of Molecular Evolution. Cambridge University Press, Cambridge.

    Google Scholar 

  • Kimura, M. & T. Ohta, 1971. On the rate of molecular evolution. J. Molec. Evol. 1: 1-17

    Article  PubMed  CAS  Google Scholar 

  • King, J.L. & T.H. Jukes, 1969. Non-Darwinian evolution. Science 164: 788-798.

    PubMed  CAS  Google Scholar 

  • Kreitman, M., 1983. Nucleotide polymorphism at the alcohol dehydrogenase locus of Drosophila melanogaster. Nature 304: 412-417.

    Article  PubMed  CAS  Google Scholar 

  • Langley, C.H. & W.M. Fitch, 1973. The constancy of evolution: a statistical analysis of the α and β aemoglobins, cytochrome c, and fibrinipeptide A, pp. 246-262 in Genetic Structure of Populations, edited by N.E. Morton, Univ. of Hawaii Press, Honolulu.

    Google Scholar 

  • Langley, C.H. & W.M. Fitch, 1974. An estimation of the constancy of the rate of molecular evolution. J. Mol. Evol. 3: 161-177.

    Article  PubMed  CAS  Google Scholar 

  • Li, W.-H., 1997. Molecular evolution. Sinauer Assoc., Inc.

  • Li, W.-H. & D. Graur, 1991. Fundamentals of Molecular Evolution. Sinauer Assoc., Inc., Sunderland.

    Google Scholar 

  • Li, W.-H., M. Gouy, P. M. Sharp, C. O'Huigin & Y.-W. Yang, 1990. Molecular phylogeny of Rodentia, Lagomorpha, Primates, Artiodactyla, and Carnivora and molecular clocks. Proc. Natl. Acad. Sci. USA 87: 6703-6707.

    Article  PubMed  CAS  Google Scholar 

  • Li, W.-H., M. Tanimura & P. M. Sharp, 1987. An evaluation of the molecular clock hypothesis using mammalian DNA sequences. J. Mol. Evol. 25: 330-342.

    PubMed  CAS  Google Scholar 

  • Margoliash, E., 1963. Primary structure and evolution of cytochrome c. Proc. Natl. Acad. Sci. USA 50: 672-679.

    Article  PubMed  CAS  Google Scholar 

  • Martin, A. P., & S. R. Palumbi, 1993. Body size, metabolic rate, generation time, and the molecular clock. Proc. Natl. Acad. Sci. USA 90: 4087-4091.

    Article  PubMed  CAS  Google Scholar 

  • Nei, M. & D. Graur, 1984. Extent of protein polymorphism and the neutral mutation theory. Evol. Biol. 17: 73-118.

    Google Scholar 

  • Ohta, T., 1973. Slightly deleterious mutant substitutions in evolution. Nature 246: 96-98.

    Article  PubMed  CAS  Google Scholar 

  • Ohta, T., 1991. Multigene families and the evolution of complexity. J. Mol. Evol. 33: 34-41.

    Article  PubMed  CAS  Google Scholar 

  • Ohta, T., 1992. The nearly neutral theory of molecular evolution. Annu. Rev. Ecol. Syst. 23: 263-286.

    Article  Google Scholar 

  • Ohta, T., 1993. An examination of the generation-time effect on molecular evolution. Proc. Natl. Acad. Sci. USA 90: 10676-10680.

    Article  PubMed  CAS  Google Scholar 

  • Ohta, T., 1995. Synonymous and nonsynonymous substitutions in mammalian genes and the nearly neutral theory. J. Mol. Evol. 40: 56-63.

    Article  PubMed  CAS  Google Scholar 

  • Ohta, T. & M. Kimura, 1971. On the constancy of the evolutionary rate of cistrons. J. Mol. Evol. 1: 18-25.

    Article  CAS  Google Scholar 

  • Riley, M., M.E. Hallas & R.C. Lewontin, 1989. Distinguishing the forces controlling variation at the Xdh locus in Drosophila pseudoobscura. Genetics 123: 359-369.

    PubMed  CAS  Google Scholar 

  • Sarich, V.M. & A.C. Wilson, 1973. Generation time and genomic evolution in Primates. Science 179: 1144-1147.

    PubMed  CAS  Google Scholar 

  • Schaeffer, S.W., C.F. Aquadro & W.W. Anderson, 1987. Restriction-map variation in the alcohol dehydrogenase region of Drosophila pseudoobscura. Mol. Biol. Evol. 4: 254-265.

    PubMed  CAS  Google Scholar 

  • Sharp, P.M., & W.-H. Li, 1989. On the rate of DNA sequence evolution in Drosophila. J. Mol. Evol. 28: 398-402.

    PubMed  CAS  Google Scholar 

  • Takahata, N. & M. Kimura, 1979. Genetic variability maintained in a finite population under mutation and autocorrelated random fluctuation of selection intensity. Proc. Natl. Acad. Sci. USA 76: 5813-5817.

    Article  PubMed  Google Scholar 

  • Takahata, N., K. Iishi & H. Matsuda, 1975. Effect of temporal fluctuation of selection coefficient on gene frequency in a population. Proc. Natl. Acad. Sci. USA 72: 4541-4545.

    Article  PubMed  CAS  Google Scholar 

  • Thomson, J.D., D.G. Higgins & T.J. Gibson, 1994. CLUSTAL W: improving the sensitivity of progressive sequence alignment through sequence weighting, positions-specific gap penalties and weight matrix choice. Nucleic Acids Res. 22: 4673-4680.

    Google Scholar 

  • Wang, D., J.L. Marsh & F.J. Ayala, 1996. Evolutionary changes inthe expression pattern of a developmentally essential gene in three Drosophila species. Proc. Natl. Acad. Sci. USA 93: 7103-7107.

    Article  PubMed  CAS  Google Scholar 

  • Wallis, M., 1996. The molecular evolution of vertebrate growth hormones: A pattern of near-stasisinterrupted by sustained bursts of rapid change. J. Mol. Evol. 43: 93-100.

    Article  PubMed  CAS  Google Scholar 

  • Wells, R.S., 1996. Nucleotide variation at the Gpdh locus in the genus Drosophila. Genetics 143: 375-384.

    PubMed  CAS  Google Scholar 

  • Wright, F., 1990. ‘The effective number of codons’ used in a gene. Gene 87: 23-39.

    Article  PubMed  CAS  Google Scholar 

  • Wu, C.-I. & W.-H. Li, 1985. Evidence for higher rates of nucleotide substitution in rodents than in man. Proc. Natl. Acad. Sci. USA 82: 1741-1745.

    Article  PubMed  CAS  Google Scholar 

  • Zeng, L.-W. & M. Kreitman, 1996a. Simple strategy for sequencing cDNA clones. Biotechniques 1996 Sep; 21(3): 446-452

    PubMed  CAS  Google Scholar 

  • Zeng, L.-W. & M. Kreitman, 1996b. Rapid and cost-effective DNA sequencing strategy for PCR products. Trends in Genetics, Technical Tips Online #TL10017.

  • Zuckerkandl, E. & L. Pauling, 1962. Molecular disease, evolution, and genetic heterogeneity, pp. 189-225 in Horizons in Biochemistry, edited by M. Kasha and B. Pullman. Academic Press. New York.

    Google Scholar 

  • Zuckerkandl, E. & L. Pauling, 1965. Evolutionary divergence and convergence in proteins, pp. 97-166 in Evolving Genes and Proteins, edited by V. Bryson and H.J. Vogel. Academic Press. New York.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Ecology and Evolution, University of Chicago, 1101 E. 57th St, Chicago, IL, 60637, USA

    Ling-Wen Zeng, Josep M. Comeron, Bin Chen & Martin Kreitman

Authors
  1. Ling-Wen Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Josep M. Comeron
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bin Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Martin Kreitman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Martin Kreitman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zeng, LW., Comeron, J.M., Chen, B. et al. The molecular clock revisited: the rate of synonymous vs. replacement change in Drosophila. Genetica 102, 369–382 (1998). https://doi.org/10.1023/A:1017035109224

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1017035109224

Search

Navigation