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      Age of the Association between Helicobacter pylori and Man


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          When modern humans left Africa ca. 60,000 years ago (60 kya), they were already infected with Helicobacter pylori, and these bacteria have subsequently diversified in parallel with their human hosts. But how long were humans infected by H. pylori prior to the out-of-Africa event? Did this co-evolution predate the emergence of modern humans, spanning the species divide? To answer these questions, we investigated the diversity of H. pylori in Africa, where both humans and H. pylori originated. Three distinct H. pylori populations are native to Africa: hpNEAfrica in Afro-Asiatic and Nilo-Saharan speakers, hpAfrica1 in Niger-Congo speakers and hpAfrica2 in South Africa. Rather than representing a sustained co-evolution over millions of years, we find that the coalescent for all H. pylori plus its closest relative H. acinonychis dates to 88–116 kya. At that time the phylogeny split into two primary super-lineages, one of which is associated with the former hunter-gatherers in southern Africa known as the San. H. acinonychis, which infects large felines, resulted from a later host jump from the San, 43–56 kya. These dating estimates, together with striking phylogenetic and quantitative human-bacterial similarities show that H. pylori is approximately as old as are anatomically modern humans. They also suggest that H. pylori may have been acquired via a single host jump from an unknown, non-human host. We also find evidence for a second Out of Africa migration in the last 52,000 years, because hpEurope is a hybrid population between hpAsia2 and hpNEAfrica, the latter of which arose in northeast Africa 36–52 kya, after the Out of Africa migrations around 60 kya.

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          We previously showed that the population history of H. pylori may be used as a marker for human migrations, including the demonstration that humans carried H. pylori out of Africa 60,000 years ago during their recent global expansions. But how long were humans infected by H. pylori prior to the out-of-Africa event? Here we showed that chimpanzees in Central-East Africa do not possess Helicobacter-like bacteria, as would have been expected for pathogen-host co-evolution over millions of years. Using H. pylori gene sequences isolated from San, a group of click-speaking hunter-gatherers, and numerous other sources, we calculated that humans have been infected with H. pylori for at least 88,000–116,000 years. Phylogenetic comparisons showed similar evolutionary histories for human and H. pylori lineages and suggest that this association stemmed from a single host jump. We showed that hpAfrica2, the most divergent H. pylori population, arose in the San and that their progenitors were the source of H. acinonychis which was acquired by large felines approximately 50,000 years ago. Furthermore, our data provided clear evidence for a recent second exodus Out of Africa in the last 52,000 years which was essential for the formation of the hybrid population that currently infects Europeans.

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          Most cited references76

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          DnaSP, DNA polymorphism analyses by the coalescent and other methods.

          DnaSP is a software package for the analysis of DNA polymorphism data. Present version introduces several new modules and features which, among other options allow: (1) handling big data sets (approximately 5 Mb per sequence); (2) conducting a large number of coalescent-based tests by Monte Carlo computer simulations; (3) extensive analyses of the genetic differentiation and gene flow among populations; (4) analysing the evolutionary pattern of preferred and unpreferred codons; (5) generating graphical outputs for an easy visualization of results. The software package, including complete documentation and examples, is freely available to academic users from: http://www.ub.es/dnasp
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            Helicobacter pylori infection.

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              TREEFINDER: a powerful graphical analysis environment for molecular phylogenetics

              Background Most analysis programs for inferring molecular phylogenies are difficult to use, in particular for researchers with little programming experience. Results TREEFINDER is an easy-to-use integrative platform-independent analysis environment for molecular phylogenetics. In this paper the main features of TREEFINDER (version of April 2004) are described. TREEFINDER is written in ANSI C and Java and implements powerful statistical approaches for inferring gene tree and related analyzes. In addition, it provides a user-friendly graphical interface and a phylogenetic programming language. Conclusions TREEFINDER is a versatile framework for analyzing phylogenetic data across different platforms that is suited both for exploratory as well as advanced studies.

                Author and article information

                Role: Editor
                PLoS Pathog
                PLoS Pathog
                PLoS Pathogens
                Public Library of Science (San Francisco, USA )
                May 2012
                May 2012
                10 May 2012
                : 8
                : 5
                [1 ]Max-Planck-Institut für Infektionsbiologie, Department of Molecular Biology, Berlin, Germany
                [2 ]Konrad Lorenz Institute for Ethology, Department of Integrative Biology and Evolution, University of Veterinary Medicine Vienna, Vienna, Austria
                [3 ]Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania, United States of America
                [4 ]Hepatology and GI-Research Laboratory, Department of Immunology, University of Pretoria, Pretoria, South Africa
                [5 ]Human Genomic Diversity and Disease Research Unit, Division of Human Genetics, School of Pathology, University of the Witwatersrand/National Health Laboratory Services, Johannesburg, South Africa
                [6 ]Environmental Research Institute and Department of Microbiology, University College Cork, Cork, Ireland
                [7 ]Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany
                [8 ]Ngamba Island Chimpanzee Sanctuary, Entebbe, Uganda
                Yale University, United States of America
                Author notes

                Conceived and designed the experiments: SWVM MA SS BL YM HS LM. Performed the experiments: SB BL SWVM LM CMS JH SS MN RPB. Analyzed the data: YM BL CMS. Contributed reagents/materials/analysis tools: MA SWVM SS HS. Wrote the paper: YM MA BL.

                Moodley et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                Page count
                Pages: 16
                Research Article
                Evolutionary Biology
                Evolutionary Genetics
                Bacterial Evolution
                Bacterial Pathogens
                Host-Pathogen Interaction

                Infectious disease & Microbiology
                Infectious disease & Microbiology


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