Selective constraints on codon usage of nuclear genes from Arabidopsis thaliana

Highly expressed nuclear genes from Arabidopsis thaliana show an increased frequency of codons that match abundant tRNAs, and it has been suggested that this reflects a selective pressure to increase translation efficiency. Here we explore the possibility that the difference in codon usage between highly expressed genes and other Arabidopsis genes is not the result of selection but, rather, arises from mutation biases. Specifically, we explore the possibility that an influence of transcription level on mutational properties coupled with a context dependency of mutations, both of which have been observed in various organisms, contribute to variation in codon-usage bias across genes. Using noncoding sites immediately flanking both high- and low-expression-coding sequences to infer context-dependent composition biases, we analyze codon-usage bias across genes. The data show that mutation bias cannot explain codon usage of high-expression genes in Arabidopsis and, surprisingly, also indicate that even low-expression genes are under selective constraints. In addition, the data indicate that the general preference for certain codons is context dependent; the composition of the 3' nucleotide, that is, the first position of the next codon, is correlated with what codon is found at an increased frequency in highly expressed genes. This context dependency indicates that selective pressure on codon usage is more complex than previously thought. Overall, the study supports previous suggestions that selection plays a significant role in determining codon usage of nuclear genes in A. thaliana.