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Genetic continuity in the last seven Millennia in human hepatitis B viruses

Hepatitis B virus (HBV) is a major human pathogen and yet the evolution history of HBV has largely remained uncertain. With a better theoretical understanding of genetic diversity, we here used a new method to examine the previously published ancient and present day HBV genomes. We identified an informative region in the HBV polymerase that is slow evolving and used it to study genetic distances among HBVs. Three ancient human HBV isolates from 4488-7074 years ago in Germany were identified as genotype G that is also presently common in the same country. We constructed a new phylogenetic tree of HBVs that placed genotype D as the most basal branch with an inferred age of ~20500 years, which is remarkably consistent with the worldwide distribution and a most parsimonious migration route of HBV genotypes today. These results help resolve the evolutionary history of HBV and provide a useful method for studying the phylogenetics of HBV and other viruses in general.