Abstract

The hepatitis B virus (HBV) is one of the most widespread human pathogens known today, yet its origin and evolutionary history are still unclear and controversial. Here, we report the analysis of three ancient HBV genomes recovered from human skeletons found at three different archaeological sites in Germany. We reconstructed two Neolithic and one medieval HBV genome by de novo assembly from shotgun DNA sequencing data. Additionally, we observed HBV-specific peptides using paleo-proteomics. Our results demonstrated that HBV has circulated in the European population for at least 7000 years. The Neolithic HBV genomes show a high genomic similarity to each other. In a phylogenetic network, they do not group with any human-associated HBV genome and are most closely related to those infecting African non-human primates. The ancient viruses appear to represent distinct lineages that have no close relatives today and possibly went extinct. Our results reveal the great potential of ancient DNA from human skeletons in order to study the long-time evolution of blood borne viruses.

Highlights

  • The hepatitis B virus (HBV) is one of the most widespread human pathogens, with worldwide over 250 million people being infected, and an annual death toll of about 1 million globally (WHO, 2017)

  • Based on the genomic sequence diversity, HBVs are currently classified into eight genotypes (A-H) and numerous subgenotypes that show distinct geographic distributions (Castelhano et al, 2017)

  • After the three ancient DNA (aDNA) extracts had appeared HBV-positive in the initial virus screening, they were subjected to deep-sequencing without any prior enrichment resulting in 367 to 419 million reads per sample (Table 1)

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Summary

Introduction

The hepatitis B virus (HBV) is one of the most widespread human pathogens, with worldwide over 250 million people being infected, and an annual death toll of about 1 million globally (WHO, 2017). A principal component analysis (PCA) of the human DNA recovered from Karsdorf (3-fold genomic coverage) revealed that the sample clusters tightly with other contemporary early Neolithic individuals from the LBK (Figure 1—figure supplement 4).

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