Evolutionary History of Helicobacter pylori Sequences Reflect Past Human Migrations in Southeast Asia

Abstract

The human population history in Southeast Asia was shaped by numerous migrations and population expansions. Their reconstruction based on archaeological, linguistic or human genetic data is often hampered by the limited number of informative polymorphisms in classical human genetic markers, such as the hypervariable regions of the mitochondrial DNA. Here, we analyse housekeeping gene sequences of the human stomach bacterium Helicobacter pylori from various countries in Southeast Asia and we provide evidence that H. pylori accompanied at least three ancient human migrations into this area: i) a migration from India introducing hpEurope bacteria into Thailand, Cambodia and Malaysia; ii) a migration of the ancestors of Austro-Asiatic speaking people into Vietnam and Cambodia carrying hspEAsia bacteria; and iii) a migration of the ancestors of the Thai people from Southern China into Thailand carrying H. pylori of population hpAsia2. Moreover, the H. pylori sequences reflect iv) the migrations of Chinese to Thailand and Malaysia within the last 200 years spreading hspEasia strains, and v) migrations of Indians to Malaysia within the last 200 years distributing both hpAsia2 and hpEurope bacteria. The distribution of the bacterial populations seems to strongly influence the incidence of gastric cancer as countries with predominantly hspEAsia isolates exhibit a high incidence of gastric cancer while the incidence is low in countries with a high proportion of hpAsia2 or hpEurope strains. In the future, the host range expansion of hpEurope strains among Asian populations, combined with human motility, may have a significant impact on gastric cancer incidence in Asia.

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

“…Given that the genetic structure retrieved among the bacterial genomes mirrors the geographic distribution of human populations Breurec et al 2011;Moodley et al 2012), the vast literature on human demographic history provides a solid basis for the study (e.g., Cavalli-Sforza et al 1994), but modeling human-H. pylori coevolution would also require knowledge of transmission dynamics and within-host variation. Despite the large number of surveys carried out, H. pylori transmission via an external source has never been demonstrated and direct contact among individuals is still considered the predominant mechanism (Brown 2000; Van Duynhoven and De Jonge 2001;Allaker et al 2002;Perry et al 2006).…”

“…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.…”

Genetic characterization of Helicobacter pylori vacA and cagA genes in Thai gastro-duodenal and hepatobiliary patients

“…However, 26% of the Western cagA sequences of Thai gastro-duodenal patients and Thai hepatobiliary patients were classified as being in the mixed cluster. Several geographic populations live together in Southeast Asia; thus, migration from various regions may be linked to diverse strains of H. pylori, as previously described by Breurecet al in 2011 [35]. These two patient groups were classified into the same group (the Thai population cluster) because they both exhibited the similarity of Western-type cagA sequences.…”

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

“…La presencia de H. pylori varía significativamente entre regiones. En los países en desarrollo hay reportes de tasas de incidencia más altas por malas condiciones de higiene, agua, alimentos contaminados y promiscuidad (4,6,9,16,18,39).…”

“…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).…”