NOTE 13F: The robustness of the genetic code may be an adaptation, which evolved to reduce sensitivity to mutation and to errors in translation—especially, the tendency of transfer RNAs to mispair at the third position. However, it may also reflect the historical origin of the code: For example, originally, U at the first position might have coded for a single hydrophobic amino acid, and only later was the code elaborated to include five different hydrophobic amino acids. These issues are discussed briefly on pages 105, 118, and 560; for a review, see Knight et al. (2001).