The 5300-year-old Helicobacter pylori genome of the Iceman

Abstract

The stomach bacterium Helicobacter pylori is one of the most prevalent human pathogens. It has dispersed globally with its human host, resulting in a distinct phylogeographic pattern that can be used to reconstruct both recent and ancient human migrations. The extant European population of H. pylori is known to be a hybrid between Asian and African bacteria, but there exist different hypotheses about when and where the hybridization took place, reflecting the complex demographic history of Europeans. Here, we present a 5300-year-old H. pylori genome from a European Copper Age glacier mummy. The "Iceman" H. pylori is a nearly pure representative of the bacterial population of Asian origin that existed in Europe before hybridization, suggesting that the African population arrived in Europe within the past few thousand years.

Fig. 1

H. pylori specific reads detected in the metagenomic datasets of the Iceman's intestine content samples. The color gradient displays the number of unambiguous H. pylori reads per million metagenomic reads. Control metagenomic datasets of the Iceman's muscle tissue and of the extraction blank were included in the analysis. The different intestinal content sampling sites are marked in the radiographic image by the following symbols: * stomach content, ○ small intestine, □ upper large intestine, Δ lower large intestine. The sampling site of the muscle control sample is highlighted in the Iceman overview picture (◇).

Fig. 2

Gene coverage and distribution of the enriched and validated Iceman H. pylori reads mapped onto the 1.6 Mb large reference genome H. pylori 26695. The coverage plot displayed in black is superimposed onto the genomic plot. The bar on the right-hand side indicates a coverage of up to 50x. The gene coding sequences are shown in blue (positive strand) and yellow (negative strand) bars in the genomic plot. The loci of the ribosomal RNA genes, of two virulence genes (vacA and cagA) and of seven genes used for MLST analysis are highlighted in the genome plot.

Fig. 3

Multilocus sequence analyses (A) Bayesian cluster analysis performed in STRUCTURE displays the population partitioning of hpEurope, hpAsia2 and hpNEAfrica and the Iceman's H. pylori strain (for details about the worldwide population partitioning of 1,603 reference H. pylori strains please refer to fig. S14). (B) STRUCTURE linkage model analysis showing the proportion of Ancestral Europe 1 (from Central Asia) and Ancestral Europe 2 (from northeast Africa) nucleotides among strains assigned to populations hpNEAfrica, hpEurope and hpAsia2 and the Iceman's H. pylori strain on the extreme right. The black arrows indicate the position of the three extant European hpAsia2 strains (C) Principal component analysis of contemporary hpNEAfrica, hpEurope and hpAsia2 strains and the Iceman's H. pylori strain.

Fig. 4

Comparative whole-genome analysis. Co-ancestry matrix showing H. pylori population structure and genetic flux. The color in the heat map corresponds to the number of genomic motifs imported from a donor genome (column) to a recipient genome (row). The inferred tree and the H. pylori strain names are displayed on the top and left of the heat map. Strain names are colored according to the H. pylori population assignment provided in the legend below the heat map. Signs for population ancestry are highlighted in the heat map with green, blue, black and white boxes.