Browsing by Author "Falush, Daniel"
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- Repeated out-of-Africa expansions of Helicobacter pylori driven by replacement of deleterious mutationsPublication . 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, DanielHelicobacter 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.
- The Helicobacter pylori Genome Project: insights into H. pylori population structure from analysis of a worldwide collection of complete genomesPublication . Thorell, Kaisa; Muñoz-Ramírez, Zilia Y.; Wang, Difei; Sandoval-Motta, Santiago; Boscolo Agostini, Rajiv; Ghirotto, Silvia; Torres, Roberto C.; HpGP Research Network; Falush, Daniel; Camargo, M. Constanza; Rabkin, Charles S.Helicobacter pylori, a dominant member of the gastric microbiota, shares coevolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated highquality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics.