Helicobacter pylori's historical journey through Siberia and the Americas

Abstract

The gastric bacterium Helicobacter pylori shares a coevolutionary history with humans that predates the out-of-Africa diaspora, and the geographical specificities of H. pylori populations reflect multiple well-known human migrations. We extensively sampled H. pylori from 16 ethnically diverse human populations across Siberia to help resolve whether ancient northern Eurasian populations persisted at high latitudes through the last glacial maximum and the relationships between present-day Siberians and Native Americans. A total of 556 strains were cultivated and genotyped by multilocus sequence typing, and 54 representative draft genomes were sequenced. The genetic diversity across Eurasia and the Americas was structured into three populations: hpAsia2, hpEastAsia, and hpNorthAsia. hpNorthAsia is closely related to the subpopulation hspIndigenousAmericas from Native Americans. Siberian bacteria were structured into five other subpopulations, two of which evolved through a divergence from hpAsia2 and hpNorthAsia, while three originated though Holocene admixture. The presence of both anciently diverged and recently admixed strains across Siberia support both Pleistocene persistence and Holocene recolonization. We also show that hspIndigenousAmericas is endemic in human populations across northern Eurasia. The evolutionary history of hspIndigenousAmericas was reconstructed using approximate Bayesian computation, which showed that it colonized the New World in a single migration event associated with a severe demographic bottleneck followed by low levels of recent admixture across the Bering Strait.

Keywords: Americas; Helicobacter pylori; Siberia; colonization; demographic model.

Fig. 1.

MLST genetic variation of H. pylori structured into 10 subpopulations of populations across Asia and the Americas. (A) Geographic distribution of 1,002 genotypes, color coded according to subpopulation. Circle positions indicate the sources of the bacterial isolates, and their sizes are proportional to the numbers of isolates. Newly sampled populations are denoted with a gray halo. (B) First two principal components of a DAPC analysis showing the three main H. pylori populations inhabiting Asia and the Americas: hpAsia2, hpEastAsia, and hpNorthAsia (dashed ovals; bold font). Five newly discovered subpopulations (hspAltai, hspUral, hspSiberia1, hspSiberia2, and hspKet) were endemic to northern and central Siberia. Seven subpopulations (smaller ovals) were nested within these major populations while three clustered in the DAPC space between populations. Newly isolated strains appear as full circles and reference strains as crosses. Key legend: color codes of all 10 subpopulations.

Fig. 2.

Coancestry matrix of admixture among 94 globally representative H. pylori genomes obtained in fineSTRUCTURE. The heat map corresponds to the number of motifs inferred to have been imported from a donor genome (column) to a recipient genome (row) by Chromopainter. The inferred tree was generated by Bayesian clustering in fineSTRUCTURE. Strain names are displayed on the top and left of the heat map and are color coded by subpopulation as in Fig. 1. Strains belonging to DAPC subpopulations hspSiberia1 and hspSiberia2 are labeled with a dashed curly bracket. Small black horizontal arrows indicate strains not clustering according to DAPC assignment. Potential sources for the genomic ancestry of Siberian strains are highlighted on the heat map in dashed boxes and color coded: gray, hpAsia2; red, hpNorthAsia; mustard green, hpEastAsia. The black dashed box shows the levels of ancestry shared among Siberian strains.

Fig. 3.

Best supported models for the evolution of newly discovered H. pylori subpopulations hspSiberia1 (A) and hspSiberia2 (B) and hspKet (C) using ABC. (A–C, Top) Sampled locations containing either source or admixed populations, the proposed migration routes of both source populations (thick arrows), and the recent colonization routes once admixture occurred (thin arrows). The transparent pie slices therefore correspond to populations that were not involved in the depicted scenario. hspSiberia1 originated through admixture between hpAsia2 and hpNorthAsia, hspSiberia2 derived via admixture between hpAsia2 and hpEastAsia, and hspKet evolved though admixture between hpNorthAsia and hspSiberia2. The median posterior estimates for admixture times (Tadm) are given for each analysis.

Fig. 4.

Reconstructing the colonization of the New World by hspIndigenousAmericas. (A) The geographic distribution of hspIndigenousAmericas subpopulations across Eurasia and the Americas. ABC was carried out on geographic populations rather than DAPC population clusters. The size of each pie represents the number of hspIndigenousAmericas strains isolated at each location, and slices represent the proportions of each DAPC-inferred populations from B, Inset. Newly sampled populations are denoted with a gray halo. (B) DAPC analysis of 123 hspIndigenousAmericas strains showing structuring into four populations. Newly sequenced strains are denoted with a filled circle, whereas reference strains are shown as crosses. An East Asian population (Hong Kong) was used as the outgroup. (C) The best supported of eight competing models with median posterior estimates. T2 is the time, in years, when the bottleneck underwent by the AM population stopped. T3 is the time, in years, when the AM population split from its common ancestor with populations ES and KC; NEa, ancestral effective population sizes; NEc, current effective population sizes; M, migration rates.