Helicobacter pylori genomes reveal Paleolithic human migration to the east end of Asia

Abstract

A virulence bacterium, Helicobacter pylori, evolved parallel to its host human, therefore, can work as a marker for tracing the human migration. We found H. pylori strains indigenous in the southernmost islands of Japanese Archipelago, Okinawa, and defined them as hspOkinawa and hpRyukyu. Genome data of the strains revealed that hspOkinawa diverged from other East Asian strains about 20,000 years ago, and that hpRyukyu diverged about 45,000 years ago. The closest strains of hpRyukyu were found from Afghanistan, Punjab, and Nepal, which suggest this strain originated in the central Asia and traveled across the Eurasian continent during Paleolithic era. The divergence date of hpRyukyu corresponds with human fossil records in Okinawa. Although it is controversial from human DNA analyses whether descendants of the Paleolithic migrants remain in the modern Japanese population, this study reveals that the bacterium of Paleolithic origin remains in the stomachs of current Japanese.

Keywords: Bacteriology; Evolutionary history; Gastroenterology; Medical Microbiology; Microbial genetics; Phylogeny.

Graphical abstract

Figure 1

Phylogenetic tree using genome data of 88 strains NJ-tree (Kimura 2-parameter) based on concatenated sequences of 619 genes (alignment length 495,102 bp. Encircled strains are those we sequenced by PacBio for this study. The squares on the right side of the tree represent population classification by STRUCTURE analysis of MLST data. The marks on the right of the boxes represent cagA genotype: ▵ cagA (−), ∗ J-Western cagA, a: Amerind cagA, e: East Asian cagA, w: Western cagA.

Figure 2

Bayesian tree of representative 24 strains The colored circles on the map indicate geographic regions of Japan and correspond to the colored circles on the H. pylori strains. Bacterial populations determined by STRUCTURE are shown by red letters. Calibration point C-1 was set at the divergence of non-African strains as lower 50 kya and upper 100 kya according to archaeological information (Bae et al., 2017; Sikora et al., 2017).

Figure 3

Putative migration path to Japan Putative migration path of hpRyukyu (A) and hspOkinawa (B). The line from Afghanistan to Nepal was colored green and gray since those strains belong to hpEurope or hpAsia2. Because hpSahul strains are not observed anywhere in the Eurasian continent, its putative path is indicated by a dotted light blue line. During the last ice age, Hokkaido was connected to the Eurasian continent via Sakhalin (A). The Okinawa islands were isolated all the time (B). HspEAsia and hspMaori spread with rice agriculture and advanced navigation systems, respectively (C).