The Impact of the Neisserial DNA Uptake Sequences on Genome Evolution and Stability

Background: Efficient natural transformation in Neisseria requires the presence of short DNA uptake sequences (DUSs). Doubts remain whether DUSs propagate by pure selfish molecular drive or are selected for 'safe sex' among conspecifics.

Results: Six neisserial genomes were aligned to identify gene conversion fragments, DUS distribution, spacing, and conservation. We found a strong link between recombination and DUS: DUS spacing matches the size of conversion fragments; genomes with shorter conversion fragments have more DUSs and more conserved DUSs; and conversion fragments are enriched in DUSs. Many recent and singly occurring DUSs exhibit too high divergence with homologous sequences in other genomes to have arisen by point mutation, suggesting their appearance by recombination. DUSs are over-represented in the core genome, under-represented in regions under diversification, and absent in both recently acquired genes and recently lost core genes. This suggests that DUSs are implicated in genome stability rather than in generating adaptive variation. DUS elements are most frequent in the permissive locations of the core genome but are themselves highly conserved, undergoing mutation selection balance and/or molecular drive. Similar preliminary results were found for the functionally analogous uptake signal sequence in Pasteurellaceae.

Conclusion: As do many other pathogens, Neisseria and Pasteurellaceae have hyperdynamic genomes that generate deleterious mutations by intrachromosomal recombination and by transient hypermutation. The results presented here suggest that transformation in Neisseria and Pasteurellaceae allows them to counteract the deleterious effects of genome instability in the core genome. Thus, rather than promoting hypervariation, bacterial sex could be regenerative.