Gain and Loss of Multiple Genes During the Evolution of Helicobacter pylori

Abstract

Sequence diversity and gene content distinguish most isolates of Helicobacter pylori. Even greater sequence differences differentiate distinct populations of H. pylori from different continents, but it was not clear whether these populations also differ in gene content. To address this question, we tested 56 globally representative strains of H. pylori and four strains of Helicobacter acinonychis with whole genome microarrays. Of the weighted average of 1,531 genes present in the two sequenced genomes, 25% are absent in at least one strain of H. pylori and 21% were absent or variable in H. acinonychis. We extrapolate that the core genome present in all isolates of H. pylori contains 1,111 genes. Variable genes tend to be small and possess unusual GC content; many of them have probably been imported by horizontal gene transfer. Phylogenetic trees based on the microarray data differ from those based on sequences of seven genes from the core genome. These discrepancies are due to homoplasies resulting from independent gene loss by deletion or recombination in multiple strains, which distort phylogenetic patterns. The patterns of these discrepancies versus population structure allow a reconstruction of the timing of the acquisition of variable genes within this species. Variable genes that are located within the cag pathogenicity island were apparently first acquired en bloc after speciation. In contrast, most other variable genes are of unknown function or encode restriction/modification enzymes, transposases, or outer membrane proteins. These seem to have been acquired prior to speciation of H. pylori and were subsequently lost by convergent evolution within individual strains. Thus, the use of microarrays can reveal patterns of gene gain or loss when examined within a phylogenetic context that is based on sequences of core genes.

Biogeography of theSulfolobus islandicuspan-genome

“…The variable genome is composed of genes not found in all strains, either because genes are gained through horizontal gene transfer or because they are differentially lost. Every unique microbial strain sequenced contains a different suite of variable genes (2,(4)(5)(6)(7)(8)(9)(10)(11). Yet, the ecological forces that define the distribution of these variable genes among strains, the sources of genetic material, and the rates at which genes are acquired and lost are unknown.…”

The complete genome sequence of a chronic atrophic gastritis Helicobacter pylori strain: Evolution during disease progression

“…ORFs that are present in the former data set and absent from the latter are listed above, and the hypothetical proteins without assignable COGs are listed in Table 7. Because Gressmann et al (33) used DNA microarrays consisting of 26695 and J99 ORFs, we converted the 1,150 ''universally present'' ORFs to HPAG1 gene identifiers to perform the comparison. Among the 1,150 ORFs, 1,146 are represented in the HPAG1 genome.…”

“…5 and 6, which are published as supporting information on the PNAS web site). The 1,025-member ChAG gene ''signature'' was further distilled by comparing it to the H. pylori ''pan-genome'' defined by Gressmann et al (33) from their analysis of 56 ''global'' H. pylori strains. Their analysis was based on DNA microarrays containing PCR products from 98% of the ORFs present in the 26695 and J99 genomes.…”

Diverse Functions of Restriction-Modification Systems in Addition to Cellular Defense

“…For example, by genome comparisons of eight chronic atrophic gastritis strains, it was found that many R-M systems are associated with this condition (204,205). Some of these chronic atrophic gastritis-associated enzymes were also found to be pH regulated (205).…”