The paradox of HBV evolution as revealed from a 16th century mummy

Author summary Hepatitis B virus (HBV) exerts formidable morbidity and mortality in humans. We used ancient DNA techniques to recover the complete genome sequence of an HBV from the mummified remains of a child discovered in the 16th century from Naples, Italy. Strikingly, our analysis of this specimen resulted in two contrasting findings: while the damage patterns lend credence to this HBV sequence being authentically 16th century, phylogenetic analysis revealed a close relationship to recently sampled viruses as expected if the sequence were a modern contaminant. We reconcile these two observations by showing that HBV evolution over the last ~450 years is characterized by a marked lack of temporal structure that hinders attempts to resolve the evolutionary time-scale of this important human pathogen.