Abstract
BackgroundHelicobacter pylori has diverged in parallel to its human host, leading to distinct phylogeographic populations. Recent evidence suggests that in the current human mixing in Latin America, European H. pylori (hpEurope) are increasingly dominant at the expense of Amerindian haplotypes (hspAmerind). This phenomenon might occur via DNA recombination, modulated by restriction-modification systems (RMS), in which differences in cognate recognition sites (CRS) and in active methylases will determine direction and frequency of gene flow. We hypothesized that genomes from hspAmerind strains that evolved from a small founder population have lost CRS for RMS and active methylases, promoting hpEurope’s DNA invasion. We determined the observed and expected frequencies of CRS for RMS in DNA from 7 H. pylori whole genomes and 110 multilocus sequences. We also measured the number of active methylases by resistance to in vitro digestion by 16 restriction enzymes of genomic DNA from 9 hpEurope and 9 hspAmerind strains, and determined the direction of DNA uptake in co-culture experiments of hspAmerind and hpEurope strains.ResultsMost of the CRS were underrepresented with consistency between whole genomes and multilocus sequences. Although neither the frequency of CRS nor the number of active methylases differ among the bacterial populations (average 8.6 ± 2.6), hspAmerind strains had a restriction profile distinct from that in hpEurope strains, with 15 recognition sites accounting for the differences. Amerindians strains also exhibited higher transformation rates than European strains, and were more susceptible to be subverted by larger DNA hpEurope-fragments than vice versa.ConclusionsThe geographical variation in the pattern of CRS provides evidence for ancestral differences in RMS representation and function, and the transformation findings support the hypothesis of Europeanization of the Amerindian strains in Latin America via DNA recombination.
Highlights
Helicobacter pylori has diverged in parallel to its human host, leading to distinct phylogeographic populations
Based on multilocus sequences (MLS), H. pylori strains can be divided into populations that are specific for the geographic origin of their human hosts [1,2,3,4]
We studied the frequencies of cognate recognition sites for 32 restriction enzymes in H. pylori strains that were assigned to different populations
Summary
Helicobacter pylori has diverged in parallel to its human host, leading to distinct phylogeographic populations. Recent evidence suggests that in the current human mixing in Latin America, European H. pylori (hpEurope) are increasingly dominant at the expense of Amerindian haplotypes (hspAmerind). This phenomenon might occur via DNA recombination, modulated by restriction-modification systems (RMS), in which differences in cognate recognition sites (CRS) and in active methylases will determine direction and frequency of gene flow. Based on multilocus sequences (MLS), H. pylori strains can be divided into populations that are specific for the geographic origin of their human hosts [1,2,3,4]. H. pylori strains isolated from Latin America Amerindian hosts showed multi-locus haplotypes of the hspAmerind and hpEurope populations in relatively equal proportions [2,5]. All H. pylori strains recovered to date from Mestizo hosts have carried European-types (s2, s1a, s1b) of vacA, while the ones recovered from Amerindian hosts exhibited similar amounts of vacA subtype s1c -clustering with East Asia-Pacific isolates- and European vacA subtype s1a and s1b [9]
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