A protein sequence is a string of amino acids, each of which is encoded by three nucleotides. There are twenty amino acids and typically sixty-one genetic codes for these amino acids. For any given protein, two sources of bias in the codon usage are present: 1) amino acid bias, which is due to the non-uniform distribution of amino acids in protein; 2) synonymous codon usage bias, which is the uneven distribution of synonymous codons, i.e., various synonymous codons are not equally used to represent a given amino acid. Within the standard genetic codes, all amino acids except Met and Trp are coded by more than one codon.
DNA sequence data from diverse organisms clearly show that synonymous codons for any amino acid are not used with equal frequency, even though choices among these codons are equivalent in terms of protein sequences (Grantham et al., 1980; Aota and Ikemura, 1986; Murray et al., 1989; Sharp et al., 1988; Shields et al., 1988; D’Onofrio et al., 1991). The relative frequency of synonymous codons varies with both the genes and the organisms. In Escherichia coli and Saccharomyces cerevisiae, codon usage correlates with tRNA content and highly expressed genes frequently use codons corresponding to the most abundant tRNAs (Ikemura, 1985). In contrast, non-coding regions of E. coli DNA showed no pronounced preference for any codon. Recently, the constraints of tRNA contents on synonymous codon choice were confirmed in 18 different unicellular organisms (Kanaya et al., 1999; Rocha et al., 2004). In addition, codon usage bias has been shown to reduce the level of error in translation of the genetic code (Archetti, 2004). In eukaryotes, codon usage bias may be affected by the selection at the pre-mRNA level (Willie and Majewski, 2004). In vertebrates, CpG suppression and DNA methylation effects (Tazi and Bird, 1990), mRNA stability (Holmquist and Filipski, 1994), codon context (Karlin and Mrazek, 1996), and species of origin (Lawrence and Ochman, 1997) have been shown to influence the codon usage bias levels as well (reviewed in Karlin et al., 1998). The codon usage bias was also associated with tissue or organ specificity (Holmquist and Filipski, 1994). However, Zhang and Li (2004) further found that the codon usage pattern of housekeeping genes does not seem to differ from that of tissue-specific genes.
Quantification of codon usage bias helps understand evolution of living organisms and genome analyses. Many different approaches have been developed in the past few decades. Most of these existing computational approaches are only suitable for the comparison of codon usage bias within a single genome. Synonymous Codon Usage Order, SCUO, is a new index developed to measure Synonymous Codon Usage Bias using information theory (Wan et al. 2003, 2004). Different from other methods, SCUO is fit for measuring synonymous codon usage bias within and across genomes. The reviews of the codon usage bias measurement methods are available in Wan et al. (2006).
About CodonO
About Synonymous Codon Usage Order (SCUO)
References
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