Helicobacter pylori Evolution: Lineage-Specific Adaptations in Homologs of Eukaryotic Sel1-Like Genes

Abstract

Geographic partitioning is postulated to foster divergence of Helicobacter pylori populations as an adaptive response to local differences in predominant host physiology. H. pylori's ability to establish persistent infection despite host inflammatory responses likely involves active management of host defenses using bacterial proteins that may themselves be targets for adaptive evolution. Sequenced H. pylori genomes encode a family of eight or nine secreted proteins containing repeat motifs that are characteristic of the eukaryotic Sel1 regulatory protein, whereas the related Campylobacter and Wolinella genomes each contain only one or two such ''Sel1-like repeat'' (SLR) genes (''slr genes''). Signatures of positive selection (ratio of nonsynonymous to synonymous mutations, d N /d S ¼ x . 1) were evident in the evolutionary history of H. pylori slr gene family expansion. Sequence analysis of six of these slr genes (hp0160, hp0211, hp0235, hp0519, hp0628, and hp1117) from representative East Asian, European, and African H. pylori strains revealed that all but hp0628 had undergone positive selection, with different amino acids often selected in different regions. Most striking was a divergence of Japanese and Korean alleles of hp0519, with Japanese alleles having undergone particularly strong positive selection (x J . 25), whereas alleles of other genes from these populations were intermingled. Homology-based structural modeling localized most residues under positive selection to SLR protein surfaces. Rapid evolution of certain slr genes in specific H. pylori lineages suggests a model of adaptive change driven by selection for fine-tuning of host responses, and facilitated by geographic isolation. Characterization of such local adaptations should help elucidate how H. pylori manages persistent infection, and potentially lead to interventions tailored to diverse human populations.

The secreted Helicobacter cysteine‐rich protein A causes adherence of human monocytes and differentiation into a macrophage‐like phenotype

“…A recent statistical analysis of Hcp sequence data supports this inference. Several Hcps show signatures of selection for amino acid change, implying adaptive evolution in different human populations [17].…”

Genome‐wide association study identifies gastric cancer susceptibility loci at 12q24.11‐12 and 20q11.21

“…Concordant with this result, 3q13.31 was validated in the meta-analysis. 53 Considering the sufficient number of samples used in our imputation analysis (6171 cases and 27 178 controls), these results would be due to differences in host genetic background and/or H. pylori subtypes 54 between Chinese and Japanese.…”

Role of eukaryotic Sel-1 like repeat containing genes in Helicobacter pylori evolution and pathogenesis.

“…Signatures of positive selection (ro > 1) were also evident in the evolutionary history of H pylori sir (sell like repeat) gene family expansion [42]. Sequence analysis of six of the nine known sir genes (hpOl60, hp0211 , hp0235, hp05l9, hp0628 and hplll7) from representative East Asian, European, and African strains revealed that all but hp0628 had been subject to positive selection, with different amino acids often being selected in different geographic regions [42]. Most striking was a divergence of Japanese and Korean alleles of hp05l9, with Japanese alleles having undergone particularly strong positive selection (ro> 25), whereas Japanese and Korean alleles of other sir and housekeeping genes were intermingled [42].…”

“…Superimposed on these, the extraordinary chronicity of infection along with the barriers to gene flow due to geographic isolation of ancestral H pylori populations cause considerable genetic drift, and thus genetic differentiation of various H pylori sUbpopulations. Such genetically isolated subpopulations are more likely to "adapt" to variations in local environments [25,42], and such adaptations could potentially explain the geographic variance found in the nature and severity of infection. However, is there a signature of such adaptations in the population genetic structure of H pylori?…”

“…Signatures of positive selection (ro > 1) were also evident in the evolutionary history of H pylori sir (sell like repeat) gene family expansion [42]. Sequence analysis of six of the nine known sir genes (hpOl60, hp0211 , hp0235, hp05l9, hp0628 and hplll7) from representative East Asian, European, and African strains revealed that all but hp0628 had been subject to positive selection, with different amino acids often being selected in different geographic regions [42].…”