Skip to main content
Log in

Synonymous and nonsynonymous rate variation in nuclear genes of mammals

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

Abstract

A maximum likelihood approach was used to estimate the synonymous and nonsynonymous substitution rates in 48 nuclear genes from primates, artiodactyls, and rodents. A codon-substitution model was assumed, which accounts for the genetic code structure, transition/transversion bias, and base frequency biases at codon positions. Likelihood ratio tests were applied to test the constancy of nonsynonymous to synonymous rate ratios among branches (evolutionary lineages). It is found that at 22 of the 48 nuclear loci examined, the nonsynonymous/synonymous rate ratio varies significantly across branches of the tree. The result provides strong evidence against a strictly neutral model of molecular evolution. Our likelihood estimates of synonymous and nonsynonymous rates differ considerably from previous results obtained from approximate pairwise sequence comparisons. The differences between the methods are explored by detailed analyses of data from several genes. Transition/transversion rate bias and codon frequency biases are found to have significant effects on the estimation of synonymous and nonsynonymous rates, and approximate methods do not adequately account for those factors. The likelihood approach is preferable, even for pairwise sequence comparison, because morerealistic models about the mutation and substitution processes can be incorporated in the analysis.

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.

Institutional subscriptions

Similar content being viewed by others

References

  • Cameron JM (1995) A method for estimating the numbers of synonymous and nonsynonymous substitutions per site. J Mol Evol 41: 1152–1159

    Google Scholar 

  • 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 11:643–647

    PubMed  CAS  Google Scholar 

  • Eyre-Walker A, Gaut BS (1997) Correlated rates of synonymous site evolution across plant genomes. Mol Biol Evol 14:455–460

    PubMed  CAS  Google Scholar 

  • Gillespie JH (1987) Molecular evolution and the neutral allele theory. Oxf Surv Evol Biol 4:10–37

    Google Scholar 

  • Gillespie JH (1989) Lineage effects and the index of dispersion of molecular evolution. Mol Biol Evol 6:636–647

    PubMed  CAS  Google Scholar 

  • Gillespie JH (1991) The causes of molecular evolution. Oxford University Press, Oxford

    Google Scholar 

  • Goldman N (1994) Variance to mean ratio, R(t), for Poisson processes on phylogenetic trees. Mol Phylogenet Evol 3:230–239

    Article  PubMed  CAS  Google Scholar 

  • Goldman N, Yang Z (1994) A codon-based model of nucleotide substitution for protein-coding DNA sequences. Mol Biol Evol 11: 725–736

    PubMed  CAS  Google Scholar 

  • Grantham R (1974) Amino acid difference formula to help explain protein evolution. Science 185:862–864

    Article  PubMed  CAS  Google Scholar 

  • Ina Y (1995) Amino acid difference formula to help explain protein evolution. Science 185:862–864

    Google Scholar 

  • Ina Y (1995) New methods for estimating the numbers of synonymous and nonsynonymous substitutions. J Mol Evol 40:190–226

    Article  PubMed  CAS  Google Scholar 

  • Ina Y (1996) Patterns of synonymous and nonsynonymous substitutions: an indicator of mechanisms of molecular evolution. J Genet 75:91–115

    Article  CAS  Google Scholar 

  • Kimura M (1968) Evolutionary rate at the molecular level. Nature 217:624–626

    Article  PubMed  CAS  Google Scholar 

  • Kimura M (1980) A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. J Mol Evol 16:111–120

    Article  PubMed  CAS  Google Scholar 

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

    Google Scholar 

  • Li W-H (1993) Unbiased estimation of the rates of synonymous and nonsynonymous substitution. J Mol Evol 36:96–99

    Article  PubMed  CAS  Google Scholar 

  • Li W-H, Wu C-I, Luo C-C (1985) A new method for estimating synonymous and nonsynonymous rates of nucleotide substitutions considering the relative likelihood of nucleotide and codon changes. Mol Biol Evol 2:150–174

    PubMed  Google Scholar 

  • McDonald JH, Kreitman M (1991) Adaptive protein evolution at the Adh locus in Drosophila. Nature 351:652–654

    Article  PubMed  CAS  Google Scholar 

  • Miyata T, Yasunaga T (1980) Molecular evolution of mRNA: a method for estimating evolutionary rates of synonymous and amino acid substitutions from homologous nucleotide sequences and its applications. J Mol Evol 16:23–36

    Article  PubMed  CAS  Google Scholar 

  • Muse SV, Gaut BS (1994) A likelihood approach for comparing synonymous and nonsynonymous nucleotide substitution rates, with application to chloroplast genome. Mol Biol Evol 11:715–724

    PubMed  CAS  Google Scholar 

  • Nei M, Gojobori T (1986) Simple methods for estimating the number of synonymous and nonsynonymous nucleotide substitutions. Mol Biol Evol 3:418–426

    PubMed  CAS  Google Scholar 

  • Nielsen R (1997) Robustness of the estimator of the index of dispersion for DNA sequences. Mol Phylogenet Evol 7:346–351

    Article  PubMed  CAS  Google Scholar 

  • Ohta T (1993) A 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 

  • Pamilo P, Bianchi NO (1993) Evolution of the Zfx and Zfy genes- rates and interdependence between the genes. Mol Biol Evol 10: 271–281

    PubMed  CAS  Google Scholar 

  • Yang Z (1997) Phylogenetic analysis by maximum likelihood (PAML), version 1.3. University of California, Berkeley, California, USA

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yang, Z., Nielsen, R. Synonymous and nonsynonymous rate variation in nuclear genes of mammals. J Mol Evol 46, 409–418 (1998). https://doi.org/10.1007/PL00006320

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/PL00006320

Key words

Navigation