Codon Bias

In this page Codon Bias and its relationships with other genomic factor will be discussed.
  • What is codon bias?
    Codon bias, the unequal use of synonymous codons for encoding amino acids (Grantham et al., 1980; Moriyama, 2003), has been found in many organisms, both prokaryotes and eukaryotes. This bias varies considerably among organisms and even within the genes of the same organism. The bias was found to be in relation with many genomic factors, such as gene length, GC-content, recombination rate, gene expression level, and density of genes (Duret and Mouchiroud, 1999; Kreitman and Comeron, 1999; Duret, 2000; Marais et al., 2001; Urrutia and Hurst, 2001, 2003; Hey and Kliman, 2002; Versteeg et al., 2003), or with other regularities in the genetic code (Karlin and Mrazek, 1996). In different species, codon bias was found to be in weak correlation with gene expression level (Ikemura, 1981; Sharp et al., 1986; Duret and Mouchiroud, 1999; Urrutia and Hurst, 2003). Two main processes were proposed to explain codonbias: natural selection acting on silent changes in DNA, mutational bias, or both. In unicellular organisms, such as E. coli and S. cerevisiae, it was found that the codons translatedby the most abundant tRNA are the most frequently used (Ikemura, 1981, 1982). In multicellular organisms, such as C. elegans (Duret, 2000) and Drosophila (Akashi, 1995; Moriyama and Powel, 1997), similar findings were found,namely, that codon bias favoring codons with high tRNA gene copy number rises with expression level, thus supporting the action of selection on codon bias to improve translation efficiency. This idea has not been confirmed in mammals (Kanaya et al., 2001). Although a weak correlation between gene expression level and codon bias has been observed in the human genome (Urrutia and Hurst, 2003), this relation has not been linked to tRNA abundance. Recently, Comeron (2004) showed that in the human genome, in the majority of amino acids with degeneracy greater than one, the codons with the most abundant tRNA gene copy numbers, also exhibit an increase in frequency in highly expressed genes compared to lowly expressed genes.