Will avilamycin convert ziracine into zerocine?

488 Emerging Infectious Diseases Vol. 7, No. 3, May–June 2001 sequencing, was also used to confirm the base calls of these 100 SNPs. The visual inspection of the electropherograms and the sequencing independent method were in good agreement and indicated that 80 (91%) of 88 successful assays of the nucleotide differences were genuine. Since our initial report, we have improved our methods for overlaying the annotation of open reading frame coordinates onto our analysis of the coordinates of nucleotide substitutions. Approximately 7% of the genome is noncoding, and approximately 15% of the substitutions are in these regions. Dr. Musser is correct in pointing out that the substitution frequency expressed in Fraser et al. (5), based on our preliminary annotation of our M. tuberculosis sequence data, is not an equivalent comparison to the synonymous substitution frequency derived by his method of sequencing a select set of genes over a wide range of M. tuberculosis strains. He uses the methods of Li et al. (6), among the most widely accepted, for the calculation of nucleotide substitution frequencies and derives a Ds value of <0.01 synonymous substitutions per 100 synonymous sites. Our preliminary data presented the frequency of total nucleotide substitutions at all positions (coding [synonymous and nonsynonymous] and noncoding) of the two recently sequenced strains, H37Rv and CDC1551. Our manuscript in preparation comparing the two M. tuberculosis strains will contain an analysis of synonymous substitutions. However, while Dr. Musser compared a select group of genes over perhaps several hundred strains, our frequency will be based on a genome-wide comparison between two strains.