Amerindian Helicobacter pylori strains go extinct, as european strains expand their host range

Abstract

We studied the diversity of bacteria and host in the H. pylori-human model. The human indigenous bacterium H. pylori diverged along with humans, into African, European, Asian and Amerindian groups. Of these, Amerindians have the least genetic diversity. Since niche diversity widens the sets of resources for colonizing species, we predicted that the Amerindian H. pylori strains would be the least diverse. We analyzed the multilocus sequence (7 housekeeping genes) of 131 strains: 19 cultured from Africans, 36 from Spanish, 11 from Koreans, 43 from Amerindians and 22 from South American Mestizos. We found that all strains that had been cultured from Africans were African strains (hpAfrica1), all from Spanish were European (hpEurope) and all from Koreans were hspEAsia but that Amerindians and Mestizos carried mixed strains: hspAmerind and hpEurope strains had been cultured from Amerindians and hpEurope and hpAfrica1 were cultured from Mestizos. The least genetically diverse H. pylori strains were hspAmerind. Strains hpEurope were the most diverse and showed remarkable multilocus sequence mosaicism (indicating recombination). The lower genetic structure in hpEurope strains is consistent with colonization of a diversity of hosts. If diversity is important for the success of H. pylori, then the low diversity of Amerindian strains might be linked to their apparent tendency to disappear. This suggests that Amerindian strains may lack the needed diversity to survive the diversity brought by non-Amerindian hosts.

Figure 1. Distribution of ABO blood groups in humans from Africa, Asia, Western countries and in Amerindians.

The blue, orange and grey bars represent respectively O, A and B allele frequencies –. The remarkable dominance of O blood groups among Amerindians from South America affects the ABO blood group recognition by H. pylori strains.

Figure 2. Pairwise genetic distances between H. pylori strains grouped by bacterial population (2A), or according to their human host (2B).

Differences in pairwise distances among strains in Fig. 2A were significant (Kruskal-Wallis test, p<2.2×10⁻¹⁶, Wilcoxon and Bonferroni; p<10⁻¹⁴) with a decreasing order hpEurope>hpAfrica1>hpEastAsia>hspAmerind. When grouped by the human host from which each strain was isolated (Fig 2B), strain diversity in Amerindians was as high as in Spanish and Mestizos (with no significant differences among them; Wilcoxon Pairwise comparison p>0.7), with a decreasing order Spaniards = Amerindians = Mestizos>Africans>Koreans. The waist of the dress-like box is the median with the waist side openings indicating the 95% interval for the median; the top represents the 3rd quartile and the bottom the 1st quartile. The interval in dashed lines represents a maximum of 1.5× interquartile range and the open circles are outliers. Permutation tests confirmed group differences in strain diversity.

Figure 3. Mosaic structure of the multilocus H. pylori sequences in representative strains.

The ancestral source of each polymorphic nucleotide is shown by a vertical line for each of the seven gene fragments in the multilocus analysis of 10 representative strains from each group (see the legend below Mestizo strains). Individual nucleotides were derived from ancestral Europe1 (grey), ancestral Europe2 (green), ancestral Africa1 (blue) and ancestral EastAsia (yellow). Nucleotides not assigned with >50% probability to any one population are indicated by white lines. African and European components can be observed in hpEurope strains from Spaniards and Mestizos, as well as in hpAfrica1 from Mestizos, while African hpAfrica1 strains and Amerindian hspAmerind strains tested were largely homogeneous.

Figure 4. Development of inter-strain genetic diversity over time as two populations recombine.

In the context of our hypothesis, a low diversity H. pylori population (P1) arose from co-evolution with the isolated Amerindian host population. With the introduction of new H. pylori strains (P2) the new population formed (P3) is more diverse than any of the source populations alone. Selection acts and strains recombine with the consequent homogenization of the population (P3′). The cycle is repeated when new populations (P4) arrive. Given time and isolation (no gene flow), population diversity will be reduced (P6). Based on their mosaic structure and high genetic distances, it seems that current H. pylori from Amerindians and Mestizos are in one of the intermediate states (P3′ or P5′). Arrows indicate introduction of new populations.