An African origin for the intimate association between humans and Helicobacter pylori

Abstract

Infection of the stomach by Helicobacter pylori is ubiquitous among humans. However, while H. pylori strains from different geographic areas are associated with clear phylogeographic differentiation1-4, the age of an association between these bacteria with humans remains highly controversial5, 6. Here we show, using sequences from a large dataset of bacterial strains that, as in humans, genetic diversity in H. pylori decreases with geographic distance from East Africa, the cradle of modern humans. We also observe similar clines of genetic isolation by distance (IBD) for both H. pylori and its human host at a worldwide scale. Like humans, simulations indicate that H. pylori seems to have spread from East Africa around 58,000 years ago. Even at more restricted geographic scales, where IBD tends to become blurred, principal component clines in H. pylori from Europe strongly resemble the classical clines for Europeans described by Cavalli-Sforza and colleagues7. Taken together, our results establish that anatomically modern humans were already infected by H. pylori prior to their migrations from Africa and demonstrate that H. pylori has remained intimately associated with their human host populations ever since.

How old are bacterial pathogens?

“…As a result of the bottlenecks associated with those migrations, and subsequent isolation by distance, the pairwise genetic distances between human populations increase with distance and their genetic diversity drops with distance from sub-Saharan Africa [26]. Quantitatively similar patterns were found for H. pylori [25], and the pairwise genetic distances between H. pylori correlated strongly with genetic distances between human mtDNA sequences from corresponding geographical areas (figure 1d). The obvious interpretation was that H. pylori have accompanied humans since their out of Africa migrations about 60 kya.…”

“…A striking number of parallels were obtained between the genetic patterns and sources of native human populations and their associations with populations of H. pylori, including native Americans who migrated from Asia across the Bering Strait (hspAmerind, a subpopulation of hpEastAsia); Austronesians who migrated from Taiwan to the Pacific (hspMaori, a subpopulation of hpEastAsia; figure 1b,c); Bantu who migrated from West Africa to East and South Africa (hpAfrica1) and the original inhabitants of the highlands of Papua New Guinea and central Australia (hpSahul) [20,22,23,25]. It is also striking that the click-speaking San, former hunter-gatherers whose mtDNA defines a basal lineage for humans, were found to be the original host of hpAfrica2, which, together with the feline H. acinonychis, forms a basal lineage within H. pylori (figure 1e).…”

The Rediscovery of H. pylori Bacteria in the Gastric Mucosa by Robin Warren, and Implications of this Finding for Human Biology and Disease

“…A wealth of research since has confirmed that link, with a surfeit of mechanistic data (including the discovery of the H. pylori gene product CagA, a unique bacterial oncoprotein), the development of animal models of H. pyloriinduced cancer, and even some, albeit underpowered, [16,17,34] Other adverse effects of H. pylori A cause of idiopathic thrombocytopenic purpura and (especially in children), obscure iron-deficiency anemia [35,36]. Associated with stunted growth and low IQ in the developing world [37] Whole genome sequencing One of the first genomes to be completely sequenced, enhancing knowledge of H. pylori biology and pathogenesis, with implications for drug and vaccine development [38] Gastric physiology, function and cell turnover Examining the effects of H. pylori eradication improved our understanding of somatostatin/gastrin/gastric acid secretion and regulation [12][13][14] among other aspects of gastric biology, including physiology, microscopic histopathology, cell biology and immunology [21,39] Human evolution Probing the genomic diversity of H. pylori among human populations has informed knowledge of human evolutionary history and migration patterns [40]. The coexistence of mammals with Helicobacter species is widespread, demonstrating an ancient and probably mutually beneficial, relationship…”

Helicobacter pylori, notre fidèle compagnon gastrique

“…Afin de résoudre cette controverse nous avons récemment analysé 769 souches de H. pylori provenant de 51 populations humaines [11]. Celles-ci ont été génotypées à plus de 1 500 sites variables distribués à travers le génome.…”