Journal of Molecular Evolution

, Volume 40, Issue 1, pp 56–63 | Cite as

Synonymous and nonsynonymous substitutions in mammalian genes and the nearly neutral theory

  • Tomoko Ohta 
Articles

Abstract

The nearly neutral theory of molecular evolution predicts larger generation-time effects for synonymous than for nonsynonymous substitutions. This prediction is tested using the sequences of 49 single-copy genes by calculating the average and variance of synonymous and nonsynonymous substitutions in mammalian star phylogenies (rodentia, artiodactyla, and primates). The average pattern of the 49 genes supports the prediction of the nearly neutral theory, with some notable exceptions.

The nearly neutral theory also predicts that the variance of the evolutionary rate is larger than the value predicted by the completely neutral theory. This prediction is tested by examining the dispersion index (ratio of the variance to the mean), which is positively correlated with the average substitution number. After weighting by the lineage effects, this correlation almost disappears for nonsynonymous substitutions, but not quite so for synonymous substitutions. After weighting, the dispersion indices of both synonymous and nonsynonymous substitutions still exceed values expected under the simple Poisson process. The results indicate that both the systematic bias in evolutionary rate among the lineages and the episodic type of rate variation are contributing to the large variance. The former is more significant to synonymous substitutions than to nonsynonymous substitutions. Isochore evolution may be similar to synonymous substitutions. The rate and pattern found here are consistent with the nearly neutral theory, such that the relative contributions of drift and selection differ between the two types of substitutions. The results are also consistent with Gillespie's episodic selection theory.

Key words

Nearly neutral theory Synonymous substitution Nonsynonymous substitution Mammalian genes 

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References

  1. Bernardi G (1989) The isochore organization of the human genome. Ann Rev Genet 23:637–661Google Scholar
  2. Bernardi G, Olofsson B, Filipski J, Zerial M, Salinas J, Cuny G, Meunier-Rotival M, Rodier F (1985) The mosaic genome of warmblooded vertebrates. Science 228:953–958Google Scholar
  3. Borriello F, Krauter KS (1991) Multiple murine α1-protease inhibitor genes show unusual evolutionary divergence. Proc Natl Acad Sci USA 88:9417–9421Google Scholar
  4. Bulmer M (1989) Estimating the variability of substitution rates. Genetics 123:615–619Google Scholar
  5. Chao L, Carr DE (1993) The molecular clock and the relationship between population size and generation time. Evolution 47:688–690Google Scholar
  6. Chen EY, Liao YC, Smith DH, Barrera-Saldana HA, Gelinas RE, Seeburg PH (1989) The human growth hormone locus: nucleotide sequence, biology and evolution. Genomics 4:479–497Google Scholar
  7. Easteal S (1990) The pattern of mammalian evolution and the relative rate of molecular evolution. Genetics 124:165–173Google Scholar
  8. Easteal S, Collet C (1994) Consistent variation in amino-acid substitution rate, despite uniformity of mutation rate: protein evolution in mammals is not neutral. Mol Biol Evol 11:643–647Google Scholar
  9. Fitch DHA, Bailey WJ, Tagle DA, Goodman M, Sieu L, Slightom JL (1991) Duplication of the γ-globin gene mediated by repetitive L1 LINE sequences in an early ancestor of simian primates. Proc Natl Acad Sci USA 88:7396–7400Google Scholar
  10. Gillespie JH (1987) Molecular evolution and the neutral allele theory. Oxf Surv Evol Biol 4:10–37Google Scholar
  11. Gillespie JH (1991) The causes of molecular evolution. Oxford University Press, OxfordGoogle Scholar
  12. Holmquist G (1992) Review article: chromosome bands, their chromatin flavors and their functional features. Am J Hum Genet 51:17–37Google Scholar
  13. Ina Y (1992) ODEN. National Institute of Genetics, Mishima, JapanGoogle Scholar
  14. Ina Y (1994) New methods for estimating the numbers of synonymous and nonsynonymous substitutions. J Mol Evol (in press)Google Scholar
  15. Irwin DM, Wilson AC (1990) Concerted evolution of ruminant stomach lysozymes. J Biol Chem 265:4944–4952Google Scholar
  16. Kimura M (1981) Possibility of extensive neutral evolution under stabilizing selection with special reference to nonrandom usage of synonymous codons. Proc Natl Acad Sci USA 78:5773–5777Google Scholar
  17. Kimura M (1983) The neutral theory of molecular evolution. Cambridge University Press, CambridgeGoogle Scholar
  18. Li W-H (1993) Unbiased estimation of the rates of synonymous and nonsynonymous substitution. J Mol Evol 36:96–99Google Scholar
  19. Li W-H, Grant D (1991) Fundamentals of molecular evolution. Sinauer, SunderlandGoogle Scholar
  20. Nei M, Gojobori T (1986) Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. Mol Biol Evol 3:418–426Google Scholar
  21. Ohta T (1973) Slightly deleterious mutant substitutions in evolution. Nature 246:96–98Google Scholar
  22. Ohta T (1974) Mutational pressure as the main cause of molecular evolution and polymorphisms. Nature 252:351–354Google Scholar
  23. Ohta T (1991) Multigene families and the evolution of complexity. J Mol Evol 33:34–41Google Scholar
  24. Ohta T (1992) The nearly neutral theory of molecular evolution. Ann Rev Syst Ecol 23:263–286Google Scholar
  25. Ohta T (1993a) An examination of the generation-time effect on molecular evolution. Proc Natl Acad Sci USA 90:10676–10680Google Scholar
  26. Ohta T (1993b) Pattern of nucleotide substitutions in growth hormone-prolactin gene family: a paradigm for evolution by gene duplication. Genetics 134:1271–1276Google Scholar
  27. Ohta T (1994a) Further examples of evolution by gene duplication revealed through DNA sequence comparisons. Genetics (in press)Google Scholar
  28. Ohta T (1994b) On hypervariability at the reactive centre of proteolytic enzymes and their inhibitors. J Mol Evol (in press)Google Scholar
  29. Parmacek MS, Bengur AR, Vara AJ, Leiden JM (1990) The structure and regulation of expression of the murine fast skeletal troponin C gene. J Biol Chem 265:15970–15976Google Scholar
  30. Rheaume C, Goodwin RL, Latimer JJ, Baumann H, Berger FG (1994) Evolution of routine α1-proteinase inhibitors: gene amplification and reactive center divergence. J Mol Evol 38:121–131Google Scholar
  31. Wallis M (1994) Variable evolutionary rates in the molecular evolution of mammalian growth hormone. J Mol Evol 38:619–627Google Scholar
  32. Wolfe KH, Sharp PM (1993) Mammalian gene evolution: nucleotide sequence divergence between mouse and rat. J Mol Evol 37:441–456Google Scholar
  33. Wolfe KH, Sharp PM, Li W-H (1989) Mutation rates differ among regions of the mammalian genome. Nature 337:283–285Google Scholar
  34. Yokoyama S, Yokoyama R (1990) Molecular evolution of visual pigment genes and other G-protein-coupled genes. In: Takahata, N, Crow JF (eds) Population biology of genes and molecules. Baifukan, TokyoGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1995

Authors and Affiliations

  • Tomoko Ohta 
    • 1
  1. 1.National Institute of GeneticsMishimaJapan

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