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Synonymous Codon Usage Is Subject To Selection in Thermophilic Bacteria
Synonymous Codon Usage Is Subject To Selection in Thermophilic Bacteria
Received May 14, 2002; Revised July 24, 2002; Accepted August 1, 2002
ABSTRACT been shown that codon usage mirrors the distribution of tRNA
abundances (2±4), indicating that the `preferred' codons are
The patterns of synonymous codon usage, both those that tend to match the more abundant anticodons. This
within and among genomes, have been extensively correlation between the abundance of codons and their
studied over the past two decades. Despite the matching anticodons suggests that relative tRNA abundance
accumulating evidence that natural selection can is the selective force that determines synonymous codon usage
shape codon usage, it has not been possible to link (2±4). Although the relative tRNA abundances may well be
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Nucleic Acids Research, 2002, Vol. 30 No. 19 4273
Table 1. Total genomic G+C contents and optimal growth temperatures for the 40 genomes analyzed in our study
the list does include two eubacterial thermophiles (Aquifex correspondence analysis (11) to characterize the patterns of
aeolicus and Thermotoga maritima) and one mesophilic codon usage among this large set of genes and to map this
archaeal species (Halobacterium sp.). These three genomes pattern onto the distribution of codons on which the pattern is
have enabled us to distinguish between the effects of based (Fig. 1A and B). Correspondence analysis was carried
environmental selection and phylogenetic history. out using the program CodonW1.4.2 (J. Peden, 2000; http://
In our analysis, we combined the genes from all 40 genomes www.molbiol.ox.ac.uk/cu/). This `transgenomic' analysis
(a total of 83 985 coding sequences) and calculated the relative allowed us to gain information on both the intra-genomic
synonymous codon usage (10) for each gene. We used and inter-genomic patterns of codon usage simultaneously.
4274 Nucleic Acids Research, 2002, Vol. 30 No. 19
DISCUSSION
By combining the genes from all 40 genomes into a single data
set, we were able to make a direct comparison between the
intra-genomic and inter-genomic variations in codon usage.
These results show very clearly that the inter-genomic
differences can be very large relative to the variations between
genes within a particular genome. This is illustrated in
Figure 2, where we can see that the distribution of values for
all genes within a genome is relatively tightly clustered around
the mean of that genome. Examination of these results can also
give us an insight into how rapidly codon usage patterns may
change over the course of evolution. For instance, by
exploiting the fact that these 40 species represent a wide
range in divergence times, we can ask if codon usage is an
Figure 5. Frequency distributions of synonymous codon usage among evolutionarily conserved character. From Figure 2, it is clear
thermophilic (red) and the mesophilic genes (blue) along the second axis of that very closely related species, e.g. different species of
inertia. We have also plotted the A.aeolicus gene frequencies as a proportion Chlamydia, have similar patterns of codon usage. When we
of all thermophilic genes (shown in green). This genome, despite being consider broader phylogenetic groupings such as the
wonder if the selection is for some general property of the protein genes: a proposal for synonymous codon choice that is optimal
mRNAs that is particularly important under conditions of high for the E. coli translational system. J. Mol. Biol., 151, 389±409.
4. Ikemura,T. (1982) Differences in synonymous codon choice patterns of
temperature, rather than for speci®c codon±anticodon yeast and correlation between the abundance of yeast transfer RNAs and
pairings. One possibility is that the process is driven by the occurrence of the respective codons in protein genes. Differences in
selection for increased mRNA stability at high temperature, synonymous codon choice patterns of yeast. J. Mol. Biol., 158, 573±597.
rather than selection for translational ef®ciency. Increased 5. Shields,D.C. and Sharp,P.M. (1987) Synonymous codon usage in
mRNA stability would result in increased levels of translated Bacillus subtilis re¯ects both translational selection and mutational
protein per mRNA molecule. Thus mRNA stability could be biases. Nucleic Acids Res., 15, 8023±8040.
6. Shields,D.C., Sharp,P.M., Higgins,D.G. and Wright,F. (1988) "Silent"
subject to similar selection pressures as translational ef®- sites in Drosophila genes are not neutral: evidence of selection among
ciency. Interestingly, both forms of selection would be more synonymous codons. Mol. Biol. Evol., 5, 704±716.
pronounced for highly expressed genes. It has been suggested 7. Stenico,M., Lloyd,A.T. and Sharp,P.M. (1994) Codon usage in
that thermophilic genomes are purine rich (21) and such a Caenorhabditis elegans: delineation of translational selection and
purine preference could affect both mRNA stability and the mutational biases. Nucleic Acids Res., 22, 2437±2446.
frequency of synonymous codons within these genomes. 8. McInerney,J.O. (1998) Replicational and transcriptional selection on
codon usage in Borrelia burgdorferi. Proc. Natl Acad. Sci. USA, 95,
In summary, we have shown that the patterns of synonym- 10698±10703.
ous codon usage within a genome can change dramatically 9. Bulmer,M. (1991) The selection-mutation-drift theory of synonymous
during the course of evolution. Our results show that the two codon usage. Genetics, 129, 897±907.
major forces affecting the broad patterns of codon usage 10. Sharp,P.M. and Li,W.-H. (1987) The selection-mutation-drift theory of
among prokaryote genomes are (i) the nucleotide composition synonymous codon usage. Nucleic Acids Res., 15, 1281±1295.