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Elife. 2018 May 10;7. pii: e36666. doi: 10.7554/eLife.36666.

Neolithic and medieval virus genomes reveal complex evolution of hepatitis B.

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Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany.
Max Planck Institute for the Science of Human History, Jena, Germany.
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
Systematic Proteomics & Bioanalytics, Institute for Experimental Medicine, Kiel University, Kiel, Germany.
Institute of Pre- and Protohistoric Archaeology, Kiel University, Kiel, Germany.
Stanley Center for Psychiatric Research, Broad Institute, Cambridge, United States.
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, United States.
Program in Medical and Population Genetics, Broad Institute of MIT & Harvard, Cambridge, United States.
Institute for Pre- and Protohistory and Near Eastern Archaeology, Heidelberg University, Heidelberg, Germany.
Heidelberg Center for the Environment, Heidelberg University, Heidelberg, Germany.
Department of Physical Anthropology, Institute of Forensic Medicine, University of Bern, Bern, Switzerland.
State Office for Heritage Management and Archaeology Saxony-Anhalt, State Museum of Prehistory, Halle, Germany.
Danube Private University, Krems, Austria.
Department of Biomedical Engineering, University Hospital Basel, University of Basel, Basel, Switzerland.
Integrative Prehistory and Archaeological Science, University of Basel, Basel, Switzerland.
Clinic for Internal Medicine, University Hospital Schleswig-Holstein, Kiel, Germany.
Contributed equally


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.


ancient DNA; ancient pathogens; genetics; genomics; hepatitis B; human evolution; infectious disease; microbiology; next generation sequencing; virus evolution

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