Transposable Element IS Hp608 of Helicobacter pylori : Nonrandom Geographic Distribution, Functional Organization, and Insertion Specificity

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Abstract
A new member of the IS 605 transposable element family, designated IS Hp608 , was found by subtractive hybridization in Helicobacter pylori . Like the three other insertion sequences (ISs) known in this gastric pathogen, it contains two open reading frames ( orfA and orfB ), each related to putative transposase genes of simpler (one-gene) elements in other prokaryotes; orfB is also related to the Salmonella virulence gene gipA . PCR and hybridization tests showed that IS Hp608 is nonrandomly distributed geographically: it was found in 21% of 194 European and African strains, 14% of 175 Bengali strains, 43% of 131 strains from native Peruvians and Alaska natives, but just 1% of 223 East Asian strains. IS Hp608 also seemed more abundant in Peruvian gastric cancer strains than gastritis strains (9 of 14 versus 15 of 45, respectively; P = 0.04). Two IS Hp608 types differing by ∼11% in DNA sequence were identified: one was widely distributed geographically, and the other was found only in Peruvian and Alaskan strains. Isolates of a given type differed by ≤2% in DNA sequence, but several recombinant elements were also found. IS Hp608 marked with a resistance gene was found to (i) transpose in Escherichia coli ; (ii) generate simple insertions during transposition, not cointegrates; (iii) insert downstream of the motif 5"-TTAC without duplicating target sequences; and (iv) require orfA but not orfB for its transposition. IS Hp608 represents a widespread family of novel chimeric mobile DNA elements whose further analysis should provide new insights into transposition mechanisms and into microbial population genetic structure and genome evolution.