Identification of New Helicobacter pylori Subpopulations in Native Americans and Mestizos From Peru

Abstract

Region-specific Helicobacter pylori subpopulations have been identified. It is proposed that the hspAmerind subpopulation is being displaced from the Americans by an hpEurope population following the conquest. Our study aimed to describe the genomes and methylomes of H. pylori isolates from distinct Peruvian communities: 23 strains collected from three groups of Native Americans (Asháninkas [ASHA, n = 9], Shimaas [SHIM, n = 5] from Amazonas, and Punos from the Andean highlands [PUNO, n = 9]) and 9 modern mestizos from Lima (LIM). Closed genomes and DNA modification calls were obtained using SMRT/PacBio sequencing. We performed evolutionary analyses and evaluated genomic/epigenomic differences among strain groups. We also evaluated human genome-wide data from 74 individuals from the selected Native communities (including the 23 H. pylori strains donors) to compare host and bacterial backgrounds. There were varying degrees of hspAmerind ancestry in all strains, ranging from 7% in LIM to 99% in SHIM. We identified three H. pylori subpopulations corresponding to each of the Native groups and a novel hspEuropePeru which evolved in the modern mestizos. The divergence of the indigenous H. pylori strains recapitulated the genetic structure of Native Americans. Phylogenetic profiling showed that Orthogroups in the indigenous strains seem to have evolved differentially toward epigenomic regulation and chromosome maintenance, whereas OGs in the modern mestizo (LIM) seem to have evolved toward virulence and adherence. The prevalence of cagA+/vacA s1i1m1 genotype was similar across populations (p = 0.32): 89% in ASHA, 67% in PUNO, 56% in LIM and 40% in SHIM. Both cagA and vacA sequences showed that LIM strains were genetically differentiated (p < 0.001) as compared to indigenous strains. We identified 642 R-M systems with 39% of the associated genes located in the core genome. We found 692 methylation motifs, including 254 population-specific sequences not previously described. In Peru, hspAmerind is not extinct, with traces found even in a heavily admixed mestizo population. Notably, our study identified three new hspAmerind subpopulations, one per Native group; and a new subpopulation among mestizos that we named hspEuropePeru. This subpopulation seems to have more virulence-related elements than hspAmerind. Purifying selection driven by variable host immune response may have shaped the evolution of Peruvian subpopulations, potentially impacting disease outcomes.

Helicobacter pylori infection causes both protective and deleterious effects in human health and disease

“…Contrastingly, those with primarily African H. pylori ancestry and African human ancestry had less severe disease ( 91 , 93 ). In the discussion of Latin America coevolution, it is important to note that that ancestral Amerindian H. pylori strains have been mostly displaced by ones of European origin ( 93 , 94 ); this may provide additional disruption. Although the role of co-evolution is difficult to definitively prove, multiple studies have shown patterns of parallel host-pathogen genetic variation that have correlated with functional and molecular changes that increase severity of disease ( 8 ).…”

Selective pressure on membrane proteins drives the evolution of Helicobacter pylori Colombian subpopulations

“…Recent studies have documented a detailed adaptive process of H. pylori to different mestizo populations in Latin American countries such as Mexico, Honduras, Nicaragua, and Peru. 5,7,15–18 We show the presence of four subpopulations inside Colombia, supported by a comprehensive genomic analysis of a considerable number of H. pylori strains from different regions of the country; such a detailed geographic substructuring of subpopulations inside a country has not been reported.…”

“…However, genome diversity of H. pylori in the Americas showed a drastic change after the arrival of Europeans and the transatlantic trade of African slaves starting 500 years ago, leading to genomes with a mosaic of admixed ancestries that have followed unique evolutionary paths. 5–7…”

Recombination events drives the emergence of Colombian Helicobacter pylori subpopulations with self-identity ancestry

“…Recent studies have documented a detailed adaptive process of H. pylori to different mestizo populations in Latin American countries such as Mexico, Honduras, Nicaragua, and Peru [ 5 , 7 , 7 , 15–17 ]. We show the presence of two subpopulations and three subgroups inside Colombia that had not been previously described and were able to identify well – differentiated clades of Colombian strains following geographical regions with a high resolution.…”

“…Thus, the first Indigenous Americans carried bacterial strains with Asian ancestry, which later evolved in isolation through a process of bacterial recombination and/or mutation. However, genome diversity of H. pylori in the Americas showed a drastic change after the arrival of Europeans and the transatlantic trade of African slaves starting 500 y ago, leading to genomes with a mosaic of admixed ancestries that have followed unique evolutionary paths [ 5–7 ].…”