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Genetics, Vol. 168, 2245-2260, December 2004, Copyright © 2004
doi:10.1534/genetics.104.030866
Intragenic Spatial Patterns of Codon Usage Bias in Prokaryotic and Eukaryotic Genomes
Hong Qin*,1,
Wei Biao Wu
,
Josep M. Comeron
,
Martin Kreitman* and
Wen-Hsiung Li*,2
* Department of Ecology and Evolution, University of Chicago, Chicago, Illinois 60637
Department of Statistics, University of Chicago, Chicago, Illinois 60637
Department of Biological Sciences, University of Iowa, Iowa City, Iowa 52242
2 Corresponding author: Department of Ecology and Evolution, University of Chicago, 1101 East 57th St., Chicago, IL 60637.
E-mail: whli{at}uchicago.edu
To study the roles of translational accuracy, translational efficiency, and the Hill-Robertson effect in codon usage bias, we studied the intragenic spatial distribution of synonymous codon usage bias in four prokaryotic (Escherichia coli, Bacillus subtilis, Sulfolobus tokodaii, and Thermotoga maritima) and two eukaryotic (Saccharomyces cerevisiae and Drosophila melanogaster) genomes. We generated supersequences at each codon position across genes in a genome and computed the overall bias at each codon position. By quantitatively evaluating the trend of spatial patterns using isotonic regression, we show that in yeast and prokaryotic genomes, codon usage bias increases along translational direction, which is consistent with purifying selection against nonsense errors. Fruit fly genes show a nearly symmetric M-shaped spatial pattern of codon usage bias, with less bias in the middle and both ends. The low codon usage bias in the middle region is best explained by interference (the Hill-Robertson effect) between selections at different codon positions. In both yeast and fruit fly, spatial patterns of codon usage bias are characteristically different from patterns of GC-content variations. Effect of expression level on the strength of codon usage bias is more conspicuous than its effect on the shape of the spatial distribution.
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