| Helicobacter pylori, a Gram-negative, curved bacterium that colonizes over half the world's population, has extensive genetic diversity on both macro and microstructural DNA levels, resulting from intragenomic rearrangements, point mutations as well as homologous recombination. The basis of such diversity in H. pylori is unclear. However, it has been hypothesized that a lack of homologs to DNA recombination/repair proteins in the H. pylori genome may be a contributing factor to the relatively low level of genomic integrity. Using assays to measure inter- and intragenomic recombination, spontaneous mutations and recovery from DNA damage, we provide evidence that the DNA repair helicase, UvrD, and recombinational repair helicases, RuvB and RecG, influence generation of H. pylori genetic diversity. Cross-species complementation assays between H. pylori and E. coli further demonstrate that these DNA repair and recombination proteins may play divergent roles dependent on host context. Furthermore, we characterize MutS2, a homolog of the mismatch repair protein MutS1, and demonstrate that it has both structural and functional divergence from MutS1. Exposure to a variety of DNA damaging agents can also result in genomic instability, and we provide evidence that DNA damage can also cause genome instability, resulting in increased frequency of deletions and spontaneous point mutations. Therefore, the free radical rich environment in which H. pylori resides, along with its relative paucity of DNA repair and recombination proteins, both contribute to diversification during the decades-long colonization of H. pylori in its human host. Such genomic diversity may facilitate adaptation to changing environments or micro-niches during prolonged colonization, creating phenotypically diverse variants through which host selection can occur. |
