Here we describe ISHp609 of Helicobacter pylori, a new member of the IS605 mobile element family that is novel and contains two genes whose functions are unknown, jhp960 and jhp961, in addition to homologs of two other H. pylori insertion sequence (IS) element genes, orfA, which encodes a putative serine recombinasetransposase, and orfB, whose homologs in other species are also often annotated as genes that encode transposases. The complete four-gene element was found in 10 to 40% of strains obtained from Africa, India, Europe, and the Americas but in only 1% of East Asian strains. Sequence comparison of 10 representative ISHp609 elements revealed higher levels of DNA sequence matches (99%) than those seen in normal chromosomal genes (88 to 98%) or in other IS elements (95 to 97% for IS605, IS606, and IS607) from the same H. pylori populations. Sequence analysis suggested that ISHp609 can insert at many genomic sites with its left end preferentially next to TAT, with no target specificity for its right end, and without duplicating or deleting target sequences. A deleted form of ISHp609, containing just jhp960 and jhp961 and 37 bp of orfA, found in reference strain J99, was at the same chromosomal site in 15 to 40% of the strains from many geographic regions but again in only 1% of the East Asian strains. The abundance and sequence homogeneity of ISHp609 and of this nonmobile remnant suggested a recent bottleneck and then rapid spread in H. pylori populations, possibly selected by the contributions of the elements to bacterial fitness.Insertion sequence (IS) elements are a diverse group of specialized DNA segments that move to new sites in prokaryotic and eukaryotic genomes by mechanisms that do not require extensive DNA sequence homology (for reviews see references 5, 7, and 19). They cause insertion mutations and genome rearrangements, affect nearby gene expression, and help mediate the spread of resistance and virulence determinants within and among species. Many IS elements specify just a single transposase protein that acts in concert with host proteins at each end of the element to mediate insertion. Other, more complex elements, such as Tn7, specify two or more proteins that act together as the transposase, plus additional proteins that help select insertion sites or affect the efficiency of transposition. Host proteins can also affect the frequency or specificity of transposition of certain elements. Many, but not all, species of elements terminate in short inverted repeats (size range, 9 to 40 bp) and generate short direct repeats of target sequences (typically 2 to 9 bp) when they transpose.Each of the four known species of IS elements in H. pylori (IS605, IS606, IS607, and ISHp608) belongs to the distinctive IS605 mobile element family, and each seems to be chimeric, containing two transposition-related genes, orfA and orfB, that may have different phylogenetic origins (12,14,16). The IS605 element family is divisible into two subfamilies based on orfA homologies; in one subfamily, represented by IS607...