Early divergent strains of Yersinia pestis in Eurasia 5,000 years ago.
The bacteria Yersinia pestis is the etiological agent of plague and has caused human pandemics with millions of deaths in historic times. How and when it originated remains contentious. Here, we report the oldest direct evidence of Yersinia pestis identified by ancient DNA in human teeth from Asia and Europe dating from 2,800 to 5,000 years ago. By sequencing the genomes, we find that these ancient plague strains are basal to all known Yersinia pestis. We find the origins of the Yersinia pestis lineage to be at least two times older than previous estimates. We also identify a temporal sequence of genetic changes that lead to increased virulence and the emergence of the bubonic plague. Our results show that plague infection was endemic in the human populations of Eurasia at least 3,000 years before any historical recordings of pandemics.
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet, Building 208, 2800 Kongens Lyngby, Denmark.
Simon
S
Rasmussen
Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Øster Voldgade 5-7, 1350 Copenhagen, Denmark.
Morten Erik
ME
Allentoft
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet, Building 208, 2800 Kongens Lyngby, Denmark.
Kasper
K
Nielsen
Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Øster Voldgade 5-7, 1350 Copenhagen, Denmark.
Ludovic
L
Orlando
Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Øster Voldgade 5-7, 1350 Copenhagen, Denmark.
Martin
M
Sikora
Department of Historical Studies, University of Gothenburg, 405 30 Gothenburg, Sweden.
Karl-Göran
KG
Sjögren
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet, Building 208, 2800 Kongens Lyngby, Denmark.
Anders Gorm
AG
Pedersen
Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Øster Voldgade 5-7, 1350 Copenhagen, Denmark.
Mikkel
M
Schubert
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet, Building 208, 2800 Kongens Lyngby, Denmark.
Alex
A
Van Dam
Section for Organismal Biology, Department of Plant and Environmental Sciences, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark.
Christian Moliin Outzen
CM
Kapel
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet, Building 208, 2800 Kongens Lyngby, Denmark.
Henrik Bjørn
HB
Nielsen
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet, Building 208, 2800 Kongens Lyngby, Denmark; Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, 2200 Copenhagen, Denmark.
Søren
S
Brunak
Division of Armenology and Social Sciences, Institute of Archaeology and Ethnography, National Academy of Sciences, 0025 Yerevan, Republic of Armenia.
Pavel
P
Avetisyan
Institute of History and Archaeology RAS (South Ural Department), South Ural State University, 454080 Chelyabinsk, Russia.
Andrey
A
Epimakhov
Orenburg Museum of Fine Arts, 460000 Orenburg, Russia.
Mikhail Viktorovich
MV
Khalyapin
Department of Archaeology and Ethnography, Yerevan State University, 0025 Yerevan, Republic of Armenia.
Artak
A
Gnuni
Department of Archaeology, University of Tartu, 51003 Tartu, Estonia.
Aivar
A
Kriiska
Institute of Archaeology, University of Wrocław, 50-139 Wrocław, Poland.
Irena
I
Lasak
Department of Evolutionary Biology, Estonian Biocentre and University of Tartu, 51010 Tartu, Estonia.
Mait
M
Metspalu
Peter the Great Museum of Anthropology and Ethnography (Kunstkamera) RAS, 199034 St. Petersburg, Russia.
Vyacheslav
V
Moiseyev
Peter the Great Museum of Anthropology and Ethnography (Kunstkamera) RAS, 199034 St. Petersburg, Russia.
Andrei
A
Gromov
Department of Historical Studies, University of Gothenburg, 405 30 Gothenburg, Sweden.
Dalia
D
Pokutta
Department of Evolutionary Biology, Estonian Biocentre and University of Tartu, 51010 Tartu, Estonia.
Lehti
L
Saag
Department of Archaeology, University of Tartu, 51003 Tartu, Estonia.
Liivi
L
Varul
Laboratory of Ethnogenomics, Institute of Molecular Biology, National Academy of Sciences, 0014 Yerevan, Armenia.
Levon
L
Yepiskoposyan
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet, Building 208, 2800 Kongens Lyngby, Denmark.
Thomas
T
Sicheritz-Pontén
Leverhulme Centre for Human Evolutionary Studies, Department of Archaeology and Anthropology, University of Cambridge, Cambridge CB2 1QH, UK.
Robert A
RA
Foley
Leverhulme Centre for Human Evolutionary Studies, Department of Archaeology and Anthropology, University of Cambridge, Cambridge CB2 1QH, UK.
Marta Mirazón
MM
Lahr
Center for Theoretical Evolutionary Genetics, University of California, Berkeley, California 94720-3140, USA.
Rasmus
R
Nielsen
Department of Historical Studies, University of Gothenburg, 405 30 Gothenburg, Sweden.
Kristian
K
Kristiansen
Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Øster Voldgade 5-7, 1350 Copenhagen, Denmark; Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK. Electronic address: ewillerslev@snm.ku.dk.
Eske
E
Willerslev
D000818:Animals; D001208:Asia; D004269:DNA, Bacterial / Q000235:genetics; D005060:Europe; D049690:History, Ancient; D049691:History, Medieval; D006801:Humans; D010930:Plague / Q000266:history / Q000382:microbiology* / Q000635:transmission; D005423:Siphonaptera / Q000382:microbiology; D014070:Tooth / Q000382:microbiology; D015010:Yersinia pestis / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*
D004269:DNA, Bacterial