Notably, a few isolates from the Canadian Arctic formed a monophyletic group within the D4 subgenotype from indigenous populations www.selleckchem.com/products/Tigecycline.html in Australia and Remote Oceania.36 The D4 strains were associated with the First Nation (Dene) population from the Western Arctic, in contrast to the subgenotype B6 found in Inuit living in the Eastern Arctic. Interestingly, the eight D4 strains were detected in different communities distantly located across the southwest Canadian

Arctic.36 Identification of monophyletic strains among the indigenous Arctic populations suggests a potential settlement of the Canadian Arctic from the Pacific. The tMRCA of D4 in the Arctic was 4.1 (95% HPD: 1.8–6.2 ka). The latter hypothesis cannot be rejected on the basis of the estimated tMRCA of D4, given that the colonization of the Pacific occurred during the last 2.0–3.0 ka.37 A well-defined geographical separation was also observed for genotypes F and H. The genetic diversity of genotype F was greater than that of H, but no geographic origin could be traced for genotype

F (Supporting Fig. S4). Notably, genotype F diversified into subgenotypes termed F1b, F2a, RXDX-106 F2b, etc., suggesting high levels of isolation for the Amerindian population carrying HBV. The branching order of primate HBV sequences indicates three independent transmission events, giving rise to the gibbon, orangutan, and chimpanzee HBV lineages, with minimum ages of 12.8, 6.9, and 8.2 ka, respectively (Figs. 1, 6). The orangutan HBV lineage is closely related to the C4 selleck compound and J human lineages. Chimpanzee-derived HBV sequences, on the other hand, are more distantly related to extant human lineages, resembling a “new” genotype within the HBV human radiation. It also suggests a cross-species event from humans to chimpanzees from an ancient human lineage that went extinct (Figs. 1, 6). This is not surprising, given the ancient nature

of potential chimpanzee ancestors. Based on the currently available HBV sequences and the nested clustering of both Asian and African ape within HBV human-derived sequences, the opposite scenario of HBV origins in humans (ape-to-human transmission) is unlikely. Our systematic survey of HBV dispersal in isolated human populations provides several lines of evidence that HBV co-diverged with modern humans. First, there is a high congruence between branching points in the HBV genealogy and those of humans—if we calibrate the HBV tree at the root node of the F/H genotypes from Amerindians using dates from genetic and archeological evidence, the estimated divergence times for subgenotypes C3 and D4 in Near and Remote Oceania are highly consistent with inferred colonization times.19 Second, our estimate of the population history of HBV over 20.0 ka closely mirrors that of humans. Third, the age of HBV infection in humans, dating back to 33.6 ka with an upper bound of ∼47.1 ka, is in agreement with the estimated coalescence time of modern non-African human mitochondrial and Y chromosomal lineages.