Human parvovirus B19 (B19V) is a ubiquitous human pathogen associated with a number of conditions, such as fifth disease in children and arthritis and arthralgias in adults. B19V is thought to evolve exceptionally rapidly among DNA viruses, with substitution rates previously estimated to be closer to those typical of RNA viruses. On the basis of genetic sequences up to ∼70 years of age, the most recent common ancestor of all B19V has been dated to the early 1800s, and it has been suggested that genotype 1, the most common B19V genotype, only started circulating in the 1960s. Here we present 10 genomes (63.9-99.7% genome coverage) of B19V from dental and skeletal remains of individuals who lived in Eurasia and Greenland from ∼0.5 to ∼6.9 thousand years ago (kya). In a phylogenetic analysis, five of the ancient B19V sequences fall within or basal to the modern genotype 1, and five fall basal to genotype 2, showing a long-term association of B19V with humans. The most recent common ancestor of all B19V is placed ∼12.6 kya, and we find a substitution rate that is an order of magnitude lower than inferred previously. Further, we are able to date the recombination event between genotypes 1 and 3 that formed genotype 2 to ∼5.0-6.8 kya. This study emphasizes the importance of ancient viral sequences for our understanding of virus evolution and phylogenetics.

Cambridge GeoGenetics Group Department of Zoology University of Cambridge CB2 3EJ Cambridge United Kingdom

Center for Pathogen Evolution Department of Zoology University of Cambridge CB2 3EJ Cambridge United Kingdom

Center for Pathogen Evolution Department of Zoology University of Cambridge CB2 3EJ Cambridge United Kingdom;

Centre for GeoGenetics Natural History Museum of Denmark University of Copenhagen 1350 Copenhagen K Denmark

Centre for GeoGenetics Natural History Museum of Denmark University of Copenhagen 1350 Copenhagen K Denmark;

Department of Anthropology University of Alberta Edmonton AB T6G 2H4 Canada

Department of Archaeology and Ancient History Uppsala University 621 67 Visby Sweden

Department of Forensic Medicine University of Copenhagen Teilum 2100 Copenhagen Denmark

Department of Historical Studies University of Gothenburg 412 61 Göteborg Sweden

Department of History Irkutsk State University 664003 Irkutsk Russia

Department of Viroscience Erasmus Medical Centre 3015 CN Rotterdam The Netherlands

Human Genetics Wellcome Trust Sanger Institute CB10 1SA Hinxton United Kingdom

Institute for History of Medicine and Foreign Languages 1st Faculty of Medicine Charles University 121 08 Prague Czech Republic

Institute of History and Cultural Heritage National Academy of Sciences 720001 Bishkek Kyrgyzstan

Institute of Molecular Biology National Academy of Sciences 0014 Yerevan Armenia

Institute of Virology Charité Universitätsmedizin Berlin 10117 Berlin Germany

Laboratory of Theriology Zoological Institute of the Russian Academy of Sciences 199034 Saint Petersburg Russia

Museum and Institute of Zoology Polish Academy of Sciences 00 679 Warsaw Poland

School of GeoScience University of Edinburgh EH8 9XP Edinburgh United Kingdom

Thames Valley Archaeological Services RG1 5NR Reading United Kingdom

The National Museum of Denmark 1220 Copenhagen Denmark

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