Genomic differentiation within East Asian Helicobacter pylori

• DOI: 10.1099/mgen.0.000676
• Publication Date: 2022-02-21T17:22:58Z
• Authors: Yuanhai You; Kaisa Thorell; Lihua He; Koji Yahara; Yoshio Yamaoka; Jeong-Heon Cha; Kazunari Murakami; Yukako Katsura; ; Ichizo Kobayashi; Daniel Falush; Jianzhong Zhang
• Keywords: 0301 basic medicine; Stomach Neoplasms* / epidemiology; bacterial pathogenesis; population genomics; Helicobacter Infections* / epidemiology; 610; Helicobacter Infections* / microbiology; outer membrane protein; Helicobacter Infections; 03 medical and health sciences; Stomach Neoplasms; Humans; multidrug efflux pump; Amino Acids; Stomach Neoplasms* / genetics; Research Articles; Phylogeny; Helicobacter pylori* / genetics; fixation index; Helicobacter pylori; gastric cancer; flagellin glycosylation; Genomics; Hydrogen Peroxide; United States; 3. Good health

The East Asian region, including China, Japan and Korea, accounts for half of gastric cancer deaths. However, different areas have contrasting gastric cancer incidences and the population structure of

Helicobacter pylori

in this ethnically diverse region is yet unknown. We aimed to investigate genomic differences in

H. pylori

between these areas to identify sequence polymorphisms associated with increased cancer risk. We analysed 381

H

.

pylori

genomes collected from different areas of the three countries using phylogenetic and population genetic tools to characterize population differentiation. The functional consequences of SNPs with a highest fixation index (Fst) between subpopulations were examined by mapping amino acid changes on 3D protein structure, solved or modelled. Overall, 329/381 genomes belonged to the previously identified hspEAsia population indicating that import of bacteria from other regions of the world has been uncommon. Seven subregional clusters were found within hspEAsia, related to subpopulations with various ethnicities, geographies and gastric cancer risks. Subpopulation-specific amino acid changes were found in multidrug exporters (hefC), transporters (frpB-4), outer membrane proteins (hopI) and several genes involved in host interaction, such as a catalase site, involved in H2O2 entrance, and a flagellin site mimicking host glycosylation. Several of the top hits, including frpB-4, hefC, alpB/hopB and hofC, have been found to be differentiated within the Americas in previous studies, indicating that a handful of genes may be key to local geographic adaptation.

H. pylori

within East Asia are not homogeneous but have become differentiated geographically at multiple loci that might have facilitated adaptation to local conditions and hosts. This has important implications for further evaluation of these changes in relation to the varying gastric cancer incidence between geographical areas in this region.