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<p>Abstract</p> <p>Background</p> <p>Genomic diversity of <it>H. pylori </it>from many different human populations is largely unknown. We compared genomes of 65 <it>H. pylori </it>strains from Nottingham, England. Molecular analysis was carried out to identify rearrangements within and outside the <it>cag</it>-pathogenicity-island (<it>cag </it>PAI) and DNA sequence divergence in candidate genes. Phylogenetic analysis was carried out based on various high-resolution genotyping techniques.</p> <p>Results</p> <p>Analyses of virulence genes (<it>cag</it>T, <it>cag</it>E, <it>cag</it>A, <it>vac</it>A, <it>ice</it>A, <it>oip</it>A and <it>bab</it>B) revealed that <it>H. pylori </it>strains from England are genetically distinct from strains obtained from other countries. The toxigenic <it>vac</it>A s1m1 genotype was found to be less common and the plasticity region cluster was found to be disrupted in all the isolates. English isolates showed a predominance of <it>ice</it>A1 alleles and a functional proinflammatory <it>oip</it>A gene. The English <it>H. pylori </it>gene pool revealed several Asian/oriental features. This included the predominance of <it>cag</it>A – <it>glr </it>(<it>cag</it>A right junction) motif types III and II (up to 42%), presence of <it>vac</it>A m1c alleles and phylogenetic affinity towards East Asian / Amerindian gene pools based on fluorescent amplified fragment length polymorphism (FAFLP) analysis and <it>glm</it>M sequence analysis.</p> <p>Conclusion</p> <p>Overall, our results demonstrated genetic affinities of <it>H. pylori </it>in England with both European and the Asian gene pools and some distinctive genetic features of virulence genes that may have evolved in this important European population.</p>