Mutation Rate Inferred From Synonymous Substitutions in a Long-Term Evolution Experiment With Escherichia coli

Abstract

The quantification of spontaneous mutation rates is crucial for a mechanistic understanding of the evolutionary process. In bacteria, traditional estimates using experimental or comparative genetic methods are prone to statistical uncertainty and consequently estimates vary by over one order of magnitude. With the advent of next-generation sequencing, more accurate estimates are now possible. We sequenced 19 Escherichia coli genomes from a 40,000-generation evolution experiment and directly inferred the point-mutation rate based on the accumulation of synonymous substitutions. The resulting estimate was 8.9 × 10(-11) per base-pair per generation, and there was a significant bias toward increased AT-content. We also compared our results with published genome sequence datasets for other bacterial evolution experiments. Given the power of our approach, our estimate represents the most accurate measure of bacterial base-substitution rates available to date.

Figure 1

Expected and observed mutational spectra for synonymous point mutations. White and black bars show the expected and observed base-pair changes, respectively. The expected values reflect the actual base-pair frequencies in the genome and the probability that a particular base-pair mutation (e.g., from C:G to T:A) produces a synonymous change.