We found a positive correlation between tRNA gene copy number and overall codon usage. For ten out of twelve amino acid isotypes which are decoded by more than one tRNA, tRNA rank order based on copy number was the same as rank based on frequency of associated codons (see Tables 3.3 and 3.4; when tRNAs were predicted to decode more than one codon, codon frequencies were summed for rankings). Glutamate and lysine, both 2-box isotypes, were the two exceptions.
tRNAs may also be ranked relative to all other tRNAs based on copy number and codon frequency. Figure 3.1 shows a consistent trend of increasing tRNA gene number with increasing codon usage (see Table 3.5 for labelled rankings). The general pattern is remarkably similar to a plot of the same type for S. cerevisiae tRNAs [Percudani et al., 1997]. The degree of similarity is somewhat surprising in view of the fact that S. cerevisiae is a single-celled eukaryote under very different metabolic stresses relative to a metazoan.
No previous studies report general intracellular tRNA levels in C. elegans, so we were not able to correlate tRNA redundancy to cellular tRNA concentrations directly. However, codon usage within highly expressed genes has been shown to correlate with tRNA concentration in S. cerevisiae [Ikemura, 1982]. In general, highly expressed genes are optimized for efficient translation, thus codon selection favors the most readily available tRNAs. By comparing tRNA gene copy number to the codons that are favored in highly expressed genes, we can infer whether intracellular tRNA concentration is influenced by gene copy number.
Tables 3.3 and 3.4 include a column, ``Preferred Codon for Highly Expr. Genes'', which indicates codons that are statistically preferred in a set of characterized, highly expressed C. elegans genes [Stenico et al., 1994]. For the 11 of 12 amino acid isotypes which are coded for by more than one tRNA, the most redundant tRNA species decodes the codons most preferred by highly expressed proteins. Glutamine was the single exception to the rule. We infer from this relationship that tRNA gene copy number is likely to be a major determinant of intracellular tRNA concentration levels.