Dating the origin and dispersal of global hepatitis B virus genotype C in humans.

Hepatitis B virus genotype C (HBV/C) is one of the most prevalent HBV strains worldwide, especially in the Western Pacific and the South-East Asia. However, the origin and evolutionary timescale of HBV/C remains largely unresolved. We analyzed the evolutionary rate and molecular clock phylogeny of 101 full-genome HBV/C sequences sampled globally using a Bayesian Markov Chain Monte Carlo (MCMC) approach. We inferred the spatiotemporal dynamics of the HBV/C worldwide by the Bayesian Stochastic Search Variable Selection (BSSVS). We found that the estimated mean evolution rate of the HBV/C genotype full-genome was 4.32 × 10 subs/site/year (95% highest posterior density 3.02 × 10 - 8.97 × 10). Phylogeographic reconstruction was able to identify a single location for the origin of the global HBV/C in Australia around A.D. 715. The subgenotype C4 diverged earliest and mainly circulated in Australia, C1 mainly in Southeast Asia, C2 mainly in East Asia and C3 in Remote Oceania. The effective number of HBV infection presented a rapid exponential increase between the 1760s and 1860s followed by a maintained high level until now. Our study, for the first time, provides an estimated timescale for the HBV/C epidemic, and brings new insight to the dispersal of HBV/C in humans globally. Based on the continuous presence of a highly effective viral population, this study provides further evidence of the challenge from a population-based molecular level to eliminate HBV by 2030, and calls for a concerted effort from policy makers, health providers, and society in the globalized world.