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Repeated out-of-Africa expansions of Helicobacter pylori driven by replacement of deleterious mutations

Publication . Thorpe, Harry A.; Tourrette, Elise; Yahara, Koji; Vale, Filipa F.; Liu, Siqi; Oleastro, Mónica; Alarcon, Teresa; Perets, Tsachi-Tsadok; Latifi-Navid, Saeid; Yamaoka, Yoshio; Martinez-Gonzalez, Beatriz; Karayiannis, Ioannis; Karamitros, Timokratis; Sgouras, Dionyssios N.; Elamin, Wael; Pascoe, Ben; Sheppard, Samuel K.; Ronkainen, Jukka; Aro, Pertti; Engstrand, Lars; Agreus, Lars; Suerbaum, Sebastian; Thorell, Kaisa; Falush, Daniel

Helicobacter pylori lives in the human stomach and has a population structure resembling that of its host. However, H. pylori fromEurope and the Middle East trace substantially more ancestry from modern African populations than the humans that carry them. Here, we use a collection of Afro-Eurasian H. pylori genomes to show that this African ancestry is due to at least three distinct admixture events. H. pylori from East Asia, which have undergone little admixture, have accumulated many more non-synonymous mutations than African strains. European and Middle Eastern bacteria have elevated African ancestry at the sites of these mutations, implying selection to remove them during admixture. Simulations show that population fitness can be restored after bottlenecks bymigration and subsequent admixture of small numbers of bacteria from non-bottlenecked populations. We conclude that recent spread of African DNA has been driven by deleterious mutations accumulated during the original out-of-Africa bottleneck.

2022-11-11Journal article

Open access

Gene content, phage cycle regulation model and prophage inactivation disclosed by prophage genomics in the Helicobacter pylori Genome Project

Publication . Vale, Filipa; HpGP Research Network; Roberts, Richard; Kobayashi, Ichizo; Camargo, Constanza; Rabkin, Charles; HpGP Research Network

Prophages can have major clinical implications through their ability to change pathogenic bacterial traits. There is limited understanding of the prophage role in ecological, evolutionary, adaptive processes and pathogenicity of Helicobacter pylori, a widespread bacterium causally associated with gastric cancer. Inferring the exact prophage genomic location and completeness requires complete genomes. The international Helicobacter pylori Genome Project (HpGP) dataset comprises 1011 H. pylori complete clinical genomes enriched with epigenetic data. We thoroughly evaluated the H. pylori prophage genomic content in the HpGP dataset. We investigated population evolutionary dynamics through phylogenetic and pangenome analyses. Additionally, we identified genome rearrangements and assessed the impact of prophage presence on bacterial gene disruption and methylome. We found that 29.5% (298) of the HpGP genomes contain prophages, of which only 32.2% (96) were complete, minimizing the burden of prophage carriage. The prevalence of H. pylori prophage sequences was variable by geography and ancestry, but not by disease status of the human host. Prophage insertion occasionally results in gene disruption that can change the global bacterial epigenome. Gene function prediction allowed the development of the first model for lysogenic-lytic cycle regulation in H. pylori. We have disclosed new prophage inactivation mechanisms that appear to occur by genome rearrangement, merger with other mobile elements, and pseudogene accumulation. Our analysis provides a comprehensive framework for H. pylori prophage biological and genomics, offering insights into lysogeny regulation and bacterial adaptation to prophages.

2024-08-12Clinical study

Open access