The cagA tree (e) (zone 3) has large d a and d b values and a low d b /d a value, primarily because of the divergence in a C-terminal region of the ORF. This region, including sequences known as EPIYA (Gln-Pro-Ile-Tyr-Ala) Cytoskeletal Signaling motif, is involved in host interaction [22, 59]. The tree here is consistent with previous results [22]. Figure 8 Genes diverged between East Asian and European strains. (A) Diagram of phylogenetic tree-based analysis. Black dots, last common ancestors of Eastern and Western strains. d a , length of the branch separating the two; d

b , average branch length of the Eastern strains. (B) Plot of gene trees based on the two distance values. Large green dot, well-defined core tree; d a *, d a for the well-defined core tree; d b *, d b for the well-defined core tree; inset box, well-defined core tree; zone 1, d b < 0.00550; zone 2, 0.00550 ≤ d b ≤ 0.0231; zone 3, d b > 0.0231; red dot, genes with positive selection for amino acid change and with d a > 2 × d a *, that selleck screening library is, d a >0.02324; (a), cheY; (b), fixQ; (c), sotA; (d), vacA; (e), cagA; (f), HP1250. N = 692 genes. (C) Representative trees with high divergence between hspEAsia and hpEurope strains. Lowest common ancestor (LCA) of hspEAsia (red) and hpEurope

(cyan). Table 5 Selected genes diverged between East Asian (hspEAsia) and European (hpEurope) H. pylori Function Genes (classified by divergence within hspEAsia)   Conserved(a) Average(b) Diverged(c) Known virulence genes   vacA, tipα cagA, hcpD Outer membrane proteins   oipA/oipA-2, vacA, vacA-4 hpaA-2, homC, hopJ/hopK, horI Lipopolysaccharide synthesis (Lewis antigen mimicry)   agt futA/futB Transport   secG , sotB

, comH , cvpA yajC Motility and chemotaxis cheY maf, fliT fliK Redox fixQ hypD, frxA, pgl, nuoF fixS, hydE Nuclease   rnhA addA, rnhB, hsdR Protein synthesis   def, prmA, tilS miaA Antibiotic-related   def, frxA , ftsA   Full list and details in Table 6, Additional file 5 (= Table S4) and text. Genes in bold were also extracted in the comparison of 6 hspEAsia vs. 5 hpEurope (Additional file 7 (= Table S5)). (a) d b d b *. Zone 3. Table 6 Genes diverged between East Asian and European Etomidate H. pylori Gene Description Representative of the gene family(a,b,c) Distance d a (d) Distance d b (e) d b zone Ilomastat concentration Reference hpaA-2 HpaA paralog HP0492(f) 0.1608 0.0253 3 [68] cagA Cag pathogenicity island protein HP0547(f) 0.1009 0.0285 3 [11]   Bacterial SH3 domain HP1250 0.0901 0.0615 3   futA, futB α-(1,3)-fucosyltransferase HP0379, HP0651 0.0553 0.0436 3 [15] sotB Sugar efflux transporter HP1185 0.0441 0.0095 2   vacA Vacuolating cytotoxin A HP0887 0.0420 0.0137 2 [67] miaA tRNA delta(2)-isopentenylpyrophosphate transferase mHP1415 0.0373 0.0241 3 [64, 144]   Hypothetical protein HPAG1_0619 0.0366 0.0540 3   hcpD Cysteine-rich protein, SLR (Sel1-like repeat) protein HP0160 0.0363 0.