Worldwide Population Structure, Long-Term Demography, and Local Adaptation of Helicobacter pylori

Abstract

Helicobacter pylori is an important human pathogen associated with serious gastric diseases. Owing to its medical importance and close relationship with its human host, understanding genomic patterns of global and local adaptation in H. pylori may be of particular significance for both clinical and evolutionary studies. Here we present the first such whole genome analysis of 60 globally distributed strains, from which we inferred worldwide population structure and demographic history and shed light on interesting global and local events of positive selection, with particular emphasis on the evolution of San-associated lineages. Our results indicate a more ancient origin for the association of humans and H. pylori than previously thought. We identify several important perspectives for future clinical research on candidate selected regions that include both previously characterized genes (e.g., transcription elongation factor NusA and tumor necrosis factor alpha-inducing protein Tipa) and hitherto unknown functional genes.KEYWORDS adaptation; neutral evolution; human pathogens H ELICOBACTER pylori is a Gram-negative bacterium that infects the mucosa of the human stomach. It was first described in the 1980s, when it was initially identified in association with chronic gastritis and later causally linked to serious gastric pathologies such as gastric cancer and ulcers (Marshall and Warren 1984;Suerbaum and Michetti 2002). It infects .80% of humans in developing countries and, although its prevalence is lower in developed countries, nearly 50% of the worldwide human population is infected (Ghose et al. 2005;Salih 2009;Salama et al. 2013).Due to its clinical and evolutionary importance, there has been considerable research on mechanisms of H. pylori transmission, as well as on the population genetics and phylogenetic relationships among global isolates. Thus far, population genetic analyses have mainly focused on seven housekeeping genes (usually referred to as multilocus sequence typing or MLST), with the primary conclusions being that H. pylori strains appear highly structured, and their phylogeographic patterns correlate consistently with that of their human hosts. Given that the H. pylori-humans association is at least 100,000 years old (Moodley et al. 2012), the current population structure of H. pylori may be regarded as mirroring past human expansions and migrations Linz et al. 2007;Breurec et al. 2011) and thus help us shed light on yet unknown dynamics of local demographic processes in human evolution. However, despite the knowledge gained thus far, the long-term global demographic history of H. pylori has never been directly inferred. The long, intimate association of H. pylori with humans suggests a history of bacterial adaptation. Considerable attention has focused on specific genes involved in modulating adaptive immunity of the host (for a review see Yamaoka 2010 andSalama et al. 2013) and on genomic changes occurring during acute and chronic H. pylori infection (Kennemann et al. 2011;Linz et a...

Rapid evolution of distinct Helicobacter pylori subpopulations in the Americas

“…However, these strains are rare even within groups with substantial Native American ancestry and may being dying out in competition with other strains, due to low diversity within the population or other factors [3]. hpEurope bacteria are themselves ancient hybrids between two populations, whose close relatives are currently found in unadmixed populations in North East Africa (hpNEAfrica) and central Asia (hpAsia2).…”

“…http://dx.doi.org/10.1101/069070 doi: bioRxiv preprint first posted online Aug. 11, 2016; hspEuropeColombia and hspAfrica1Nicaragua populations have elevated hspAfrica1SAfrica proportions, consistent with recent genetic mixture (Figure 2A). (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11) …”

Coevolución genética Homo sapiens-Helicobacter pylori y sus implicaciones en el desarrollo del cáncer gástrico: una revisión sistemática

“…Las mayores tasas corresponden a las zonas montañosas del Litoral Pacífico, incluidos Chile, Ecuador, Perú, Costa Rica y Colombia (1,2). Las variaciones interpoblacionales y étnicas en la progresión de la enfermedad pueden atribuirse a factores de riesgo tanto ambientales, como genéticos, de origen somático o germinal (3,4).…”

“…La bacteria Helicobacter pylori coevoluciona con el hombre desde su origen y es muy común en el microbioma intestinal -infecta a más del 50% de la población mundial y contribuye en un ~20% al desarrollo de enfermedades gás-tricas y CG (4,7,(12)(13)(14). Desde 1994, es considerada por la Agencia Internacional para la Investigación en Cáncer (IARC) como un carcinógeno tipo I, por ser la principal causa de cáncer relacionada con la infección en hombres y la segunda en mujeres después del cáncer de cuello uterino (1,8).…”

“…Dado que la filogenia étnico-geográfica de este pató-geno se define con cepas específicas para grandes áreas continentales y patrones geográficos de diversidad genética, paralelos a los de la diversidad humana (1,(3)(4)(5)(6)(7)(8)(9)(10)(11)(12), algunos estudios sugieren que las interacciones entre el genoma del huésped-patógeno, la disrupción en el proceso de coevolución por infección con cepas de origen ancestral distinto al del huésped, la transferencia horizontal de segmentos de genes que no han coevolucionado con sus anfitriones y la selección positiva de cepas introducidas podrían generar una alteración de la selección para virulencia y perturbar el proceso de coevolución, lo que explicaría las altas tasas de incidencia de CG en poblaciones humanas con alta diversidad genética como la colombiana, que posee una mezcla genética compleja de diferentes proporciones -amerindia, europea y africana-, debida a un proceso reciente de mezcla intercontinental (17).…”