Codon volatility does not detect selection

Arising from: J. B. Plotkin, J. Dushoff & H. B. Fraser Nature428, 942–945 (2004); see also communication from Hahn et al.; Nielsenet al.; Plotkin et al. reply Plotkin et al.1 introduce a method to detect selection that is based on an index called codon volatility and that uses only the sequence of a single genome, claiming that this method is applicable to a large range of sequenced organisms1. Volatility for a given codon is the ratio of non-synonymous codons to all sense codons accessible by one point mutation. The significance of each gene's volatility is assessed by comparison with a simulated distribution of 106 synonymous versions of each gene, with synonymous codons drawn randomly from average genome frequencies. Here we re-examine their method and data and find that codon volatility does not detect selection, and that, even if it did, the genomes of Mycobacterium tuberculosis and Plasmodium falciparum, as well as those of most sequenced organisms, do not meet the assumptions necessary for application of their method.