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.

Figure 1. The distribution and phylogenetic differentiation of European (hpEurope) H. pylori isolates in Southeast Asia.

(A) Map of sampling locations of hpEurope haplotypes in Southeast Asia. (B) The Neighbor-joining tree generated from pair-wise F_ST values indicates a common, non-European origin of the Southeast Asian hpEurope strains.

Figure 2. hpEastAsia H. pylori strains in Southeast Asia.

(A) Map of sampling locations of hspEAsia haplotypes in Southeast Asia. The size of the chart indicates the number of hspEAsia haplotypes at each sampling location. (B) Neighbor-joining tree from pair-wise F_ST values of hpEastAsia haplotypes rooted with haplotypes of the population hpSahul. (C) Neighbor-joining tree of pair-wise F_ST values of the subpopulation hspEAsia.

Figure 3. The distribution hpAsia2 haplotypes in Southeast Asia.

(A) Sampling locations of hpAsia2 haplotypes in Southeast Asia. (B) A neighbor-joining tree constructed from pair-wise F_ST values of hpAsia2 haplotypes indicates a common ancestral origin of hpAsia2 strains from Thailand, Bangladesh, Malaysia and the Philippines.

Figure 4. Human migrations in Southeast Asia as proposed from H. pylori sequences.

I) An ancient migration from India distributed hpEurope bacteria in Southeast Asia. II) An ancient migration of Austro-Asiatic speakers from China carrying bacteria of the population hspEAsia. III) A migration of Tai-Kadai speakers introduced hpAsia2 bacteria in Thailand. IV) Recent migrations of Chinese from the Guangdong and Fujian provinces spread hspEAsia bacteria in Malaysia and Thailand within the last 200 years. V) Recent migrations of Indians to Malaysia brought both hpEurope and hpAsia2 bacteria to Malaysia.