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Molecular Biology and Evolution, Vol 2, 150-174, Copyright © 1985 by Society for Molecular Biology and Evolution


REVIEW ARTICLE

A new method for estimating synonymous and nonsynonymous rates of nucleotide substitution considering the relative likelihood of nucleotide and codon changes

WH Li, CI Wu and CC Luo
Center for Demographic and Population Genetics, University of Texas, Houston 77225.

A new method is proposed for estimating the number of synonymous and nonsynonymous nucleotide substitutions between homologous genes. In this method, a nucleotide site is classified as nondegenerate, twofold degenerate, or fourfold degenerate, depending on how often nucleotide substitutions will result in amino acid replacement; nucleotide changes are classified as either transitional or transversional, and changes between codons are assumed to occur with different probabilities, which are determined by their relative frequencies among more than 3,000 changes in mammalian genes. The method is applied to a large number of mammalian genes. The rate of nonsynonymous substitution is extremely variable among genes; it ranges from 0.004 X 10(-9) (histone H4) to 2.80 X 10(-9) (interferon gamma), with a mean of 0.88 X 10(-9) substitutions per nonsynonymous site per year. The rate of synonymous substitution is also variable among genes; the highest rate is three to four times higher than the lowest one, with a mean of 4.7 X 10(-9) substitutions per synonymous site per year. The rate of nucleotide substitution is lowest at nondegenerate sites (the average being 0.94 X 10(-9), intermediate at twofold degenerate sites (2.26 X 10(-9)). and highest at fourfold degenerate sites (4.2 X 10(-9)). The implication of our results for the mechanisms of DNA evolution and that of the relative likelihood of codon interchanges in parsimonious phylogenetic reconstruction are discussed.
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Science, May 3, 2002; 296(5569): 864 - 868.
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Hum Mol GenetHome page
L. Tiret, O. Poirier, V. Nicaud, S. Barbaux, S.-M. Herrmann, C. Perret, S. Raoux, C. Francomme, G. Lebard, D. Tregouet, et al.
Heterogeneity of linkage disequilibrium in human genes has implications for association studies of common diseases
Hum. Mol. Genet., February 1, 2002; 11(4): 419 - 429.
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GeneticsHome page
J. Hey and R. M. Kliman
Interactions Between Natural Selection, Recombination and Gene Density in the Genes of Drosophila
Genetics, February 1, 2002; 160(2): 595 - 608.
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Proc. Natl. Acad. Sci. USAHome page
F. Chiaromonte, S. Yang, L. Elnitski, V. B. Yap, W. Miller, and R. C. Hardison
Association between divergence and interspersed repeats in mammalian noncoding genomic DNA
PNAS, November 15, 2001; (2001) 251423898.
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Mol Biol EvolHome page
D. A. Liberles
Evaluation of Methods for Determination of a Reconstructed History of Gene Sequence Evolution
Mol. Biol. Evol., November 1, 2001; 18(11): 2040 - 2047.
[Abstract] [Full Text] [PDF]


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Mol Biol EvolHome page
M. F. Santibanez-Koref, R. Gangeswaran, and J. M. Hancock
A Relationship Between Lengths of Microsatellites and Nearby Substitution Rates in Mammalian Genomes
Mol. Biol. Evol., November 1, 2001; 18(11): 2119 - 2123.
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Mol Biol EvolHome page
N. G. C. Smith and A. Eyre-Walker
Nucleotide Substitution Rate Estimation in Enterobacteria: Approximate and Maximum-Likelihood Methods Lead to Similar Conclusions
Mol. Biol. Evol., November 1, 2001; 18(11): 2124 - 2126.
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Proc. Natl. Acad. Sci. USAHome page
M. Barrier, R. H. Robichaux, and M. D. Purugganan
Accelerated regulatory gene evolution in an adaptive radiation
PNAS, August 17, 2001; (2001) 181257698.
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Mol Biol EvolHome page
A. Munte, M. Aguade, and C. Segarra
Changes in the Recombinational Environment Affect Divergence in the yellow Gene of Drosophila
Mol. Biol. Evol., June 1, 2001; 18(6): 1045 - 1056.
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Mol Biol EvolHome page
A.-M. K. Pedersen and J. L. Jensen
A Dependent-Rates Model and an MCMC-Based Methodology for the Maximum-Likelihood Analysis of Sequences with Overlapping Reading Frames
Mol. Biol. Evol., May 1, 2001; 18(5): 763 - 776.
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J. Gen. Virol.Home page
P. Simmonds
2000 Fleming Lecture. The origin and evolution of hepatitis viruses in humans
J. Gen. Virol., April 1, 2001; 82(4): 693 - 712.
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Mol Biol EvolHome page
T. R. Schmidt, W. Wu, M. Goodman, and L. I. Grossman
Evolution of Nuclear- and Mitochondrial-Encoded Subunit Interaction in Cytochrome c Oxidase
Mol. Biol. Evol., April 1, 2001; 18(4): 563 - 569.
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Proc. Natl. Acad. Sci. USAHome page
E. A. Gaucher, M. M. Miyamoto, and S. A. Benner
Function-structure analysis of proteins using covarion-based evolutionary approaches: Elongation factors
PNAS, January 16, 2001; 98(2): 548 - 552.
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Mol Biol EvolHome page
R. M. Adkins, A. Nekrutenko, and W.-H. Li
Bushbaby Growth Hormone Is Much More Similar to Nonprimate Growth Hormones than to Rhesus Monkey and Human Growth Hormones
Mol. Biol. Evol., January 1, 2001; 18(1): 55 - 60.
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J. Virol.Home page
H.-M. Liu, D.-P. Zheng, L.-B. Zhang, M. S. Oberste, M. A. Pallansch, and O. M. Kew
Molecular Evolution of a Type 1 Wild-Vaccine Poliovirus Recombinant during Widespread Circulation in China
J. Virol., December 1, 2000; 74(23): 11153 - 11161.
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GeneticsHome page
J. P. Bielawski, K. A. Dunn, and Z. Yang
Rates of Nucleotide Substitution and Mammalian Nuclear Gene Evolution: Approximate and Maximum-Likelihood Methods Lead to Different Conclusions
Genetics, November 1, 2000; 156(3): 1299 - 1308.
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Mol Biol EvolHome page
J.-N. Volff, C. Korting, and M. Schartl
Multiple Lineages of the Non-LTR Retrotransposon Rex1 with Varying Success in Invading Fish Genomes
Mol. Biol. Evol., November 1, 2000; 17(11): 1673 - 1684.
[Abstract] [Full Text] [PDF]



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