Genome-Wide Biases in the Rate and Molecular Spectrum of Spontaneous Mutations in <i>Vibrio cholerae</i> and <i>Vibrio fischeri</i>

The vast diversity in nucleotide composition and architecture among bacterial genomes may be partly explained by inherent biases in the rates and spectra of spontaneous mutations. Bacterial genomes with multiple chromosomes are relatively unusual but some are relevant to human health, none more so than the causative agent of cholera, &lt;it&gt;Vibrio cholerae&lt;/it&gt;. Here, we present the genome-wide mutation spectra in wild-type and mismatch repair (MMR) defective backgrounds of two &lt;it&gt;Vibrio&lt;/it&gt; species, the low-%GC squid symbiont &lt;it&gt;V. fischeri&lt;/it&gt; and the pathogen &lt;it&gt;V. cholerae&lt;/it&gt;, collected under conditions that greatly minimize the efficiency of natural selection. In apparent contrast to their high diversity in nature, both wild-type &lt;it&gt;V. fischeri&lt;/it&gt; and &lt;it&gt;V. cholerae&lt;/it&gt; have among the lowest rates for base-substitution mutations (bpsms) and insertion–deletion mutations (indels) that have been measured, below 10−3/genome/generation. &lt;it&gt;Vibrio fischeri&lt;/it&gt; and &lt;it&gt;V. cholerae&lt;/it&gt; have distinct mutation spectra, but both are AT-biased and produce a surprising number of multi-nucleotide indels. Furthermore, the loss of a functional MMR system caused the mutation spectra of these species to converge, implying that the MMR system itself contributes to species-specific mutation patterns. Bpsm and indel rates varied among genome regions, but do not explain the more rapid evolutionary rates of genes on chromosome 2, which likely result from weaker purifying selection. More generally, the very low mutation rates of &lt;it&gt;Vibrio&lt;/it&gt; species correlate inversely with their immense population sizes and suggest that selection may not only have maximized replication fidelity but also optimized other polygenic traits relative to the constraints of genetic drift.