Phylogeographic diversity and mosaicism of the integrative and conjugative elements.

Background: The genome of the gastric pathogen is characterised by considerable variation of both gene sequence and content, much of which is contained within three large genomic islands comprising the pathogenicity island (PAI) and two mobile integrative and conjugative elements (ICEs) termed and . All three islands are implicated as virulence factors, although whereas the PAI is well characterised, understanding of how the elements influence interactions with different human hosts is significantly confounded by limited definition of their distribution, diversity and structural representation in the global population.

Results: To gain a global perspective of ICE population dynamics we established a bioinformatics workflow to extract and precisely define the full pan-gene content contained within a global collection of 221 draft and complete genome sequences. Complete (ca. 35-55kbp) and remnant ICE clusters were reconstructed from a dataset comprising > 12,000 genes, from which orthologous gene complements and distinct alleles descriptive of different ICE types were defined and classified in comparative analyses. The genetic variation within defined ICE modular segments was subsequently used to provide a complete description of ICE diversity and a comprehensive assessment of their phylogeographic context. Our further examination of the apparent ICE modular types identified an ancient and complex history of ICE residence, mobility and interaction within particular phylogeographic lineages and further, provided evidence of both contemporary inter-lineage and inter-species ICE transfer and displacement.

Conclusions: Our collective results establish a clear view of ICE diversity and phylogeographic representation in the global population, and provide a robust contextual framework for elucidating the functional role of the ICEs particularly as it relates to the risk of gastric disease associated with different ICE genotypes.