Developmental stage and level of codon usage bias in Drosophila

Codon usage bias (CUB) is a ubiquitous observation in molecular evolution. As a model, Drosophila has been particularly well-studied and indications show that selection at least partially controls codon usage, probably through selection for translational efficiency. Although many aspects of Drosophila CUB have been studied, this is the first study relating codon usage to development in this holometabolous insect with very different life stages. Here we ask the question: What developmental stage of Drosophila melanogaster has the greatest CUB? Genes with maximum expression in the larval stage have the greatest overall CUB when compared with embryos, pupae, and adults. (The same pattern was observed in Drosophila pseudoobscura, see Supplementary Material online.) We hypothesize this is related to the very rapid growth of larvae, placing increased selective pressure to produce large amounts of protein: a 300-fold increase requiring an approximate doubling of protein content every 10 h. Genes with highest expression in adult males and early embryos, stages with the least de novo protein synthesis, display the least CUB. These results are consistent with the hypothesis that CUB is caused (at least in part) by selection for efficient protein production. This seems to hold on the individual gene level (highly expressed genes are more biased than lowly expressed genes) as well as on a more global scale where genes with maximum expression during times of very rapid growth and protein synthesis are more biased than genes with maximum expression during times of low growth.