Differential genomic variation between short- and long-term bacterial evolution revealed by ultradeep sequencing.

Mutation and selection are both thought to impact significantly the nucleotide composition of bacterial genomes. Earlier studies have compared closely related strains to obtain mutation patterns based on the hypothesis that these bacterial strains had diverged so recently that selection will not have had enough time to play its role. In this study, we used a SOLiD autosequencer that was based on a dual-base encoding scheme to sequence the genome of Staphylococcus aureus with a mapping coverage of over 5,000×. By directly counting the variation obtained from these ultradeep sequencing reads, we found that A → G was the predominant single-base substitution and 1 bp deletions were the major small indel. These patterns are completely different from those obtained by comparison of closely related S. aureus strains, where C → T accounted for a larger proportion of mutations and deletions were shown to occur at an almost equal frequency to insertion. These findings suggest that the genomic differences between closely related bacterial strains have already undergone selection and are therefore not representative of spontaneous mutation.