70 ± 0.04 0.18 ± 0.01 3.53 ± 0.01 0.11 0.05 HpyCH4V TGCA 3.85 ± 0.75 3.70 ± 0.03 3.45 ± 0.03 Selleckchem STI571 3.53 ± 0.03 1.04 0.98 HpyCI GATATC 0.00 ± 0.03 0.31 ± 0.01 0.02 ± 0.00 0.33 ± 0.00 0.01 0.07 CDK inhibitors in clinical trials HpyF10VI GCNNNNNNNGC 2.70 ± 0.35 1.96 ± 0.04 2.97 ± 0.09 1.43 ± 0.02 1.38 2.07 HpyF14I CGCG 2.26 ± 0.46 1.96 ± 0.05 1.55 ± 0.05 1.43 ± 0.02 1.15 1.08 HpyF2I CTRYG 1.16 ± 0.17 0.92 ± 0.01 0.37 ± 0.01 0.88 ± 0.00 1.26 0.42 HpyF36IV GDGCHC 0.20 ± 0.21 1.22 ± 0.03 0.31 ± 0.01 0.93 ± 0.01 0.16 0.33 Hpy44II GGNNCC 1.21 ± 0.38 1.96 ± 0.05 0.44 ± 0.00

1.43 ± 0.02 0.62 0.31 HpyII GAAGA 2.29 ± 0.23 2.14 ± 0.03 2.87 ± 0.02 2.16 ± 0.00 1.07 1.33 HpyIP CATG 4.63 ± 0.25 3.70 ± 0.03 4.43 ± 0.04 3.53 ± 0.01 1.25 1.25 HpyIV GANTC 1.70 ± 0.25 3.70 ± 0.04 1.66 ± 0.02 3.53 ± 0.01 0.46 0.47 HpyNI CCNGG 2.04 ± 0.30 1.96 ± 0.05 0.87 ± 0.02 1.43 ± 0.02 1.04 0.61 HpyPORF1389P GAATTC 0.01 ± 0.05 0.31 ± 0.01 0.11 ± 0.00 0.33 ± 0.00 0.03 0.32 HpyV TCGA 0.95 ± 0.25 3.70 ± 0.03 0.18 ± 0.00 3.53 ± 0.01

0.26 0.05 HpyVIII CCGG 1.92 ± 0.30 1.96 ± 0.04 1.06 ± 0.02 1.43 ± 0.02 0.98 0.74 aRestriction endonucleases with palindromic recognition sites are indicated in bold. O/E ratios that are significantly (p-value <0.05) different from unity are highlighted in bold and bigger font. cExclusively underrepresented

in hpEurope Entospletinib manufacturer MLS. The observed/expected (O/E) ratio indicates deviation from the expectation based on G + C ratio. O/E ratios were highly similar for the WGS and MLS (R2 = 0.87, p < 0.001), without any differences by haplotype. Analysis of the hpEurope and hspAmerind sequences showed that 10 of the 32 cognate restriction sites were underrepresented in MLS and 6 of those sites were also underrepresented in WGS (defined as O/E ≤ 0.5 and Chi Square p-value ≤ 0.005; Table 2). One exception, Hpy166III (cognate site: CCTC) was exclusively underrepresented in hpEurope MLS, but not in the hspAmerind nor in WGS. The underrepresented sites Baricitinib varied in their C + G content from 33.3 to 75%. Most (9) of those 10 underrepresented sites were palindromic [28–30] (Table 2). Conversely, only one cognate recognition site: Hpy99III (cognate site: GCGC), was strongly overrepresented (O/E ≥ 2 and Chi Square p-value ≤ 0.005) in both hpEurope/hspAmerind MLS and WGS (Table 2). Overall, similar results were found when analyzing hspEAsia and hspWAfrica strains (data not shown). In summary, the H. pylori genome has mostly evolved to avoid RMS cognate recognition sites.