Download Ancient Pathogen Genomics: What we learn from historic

y
r
a
r
b
i
L
e r
D ho
I
t
M
u
C
a
S
y
E
b
Ancient Pathogen Genomics:
What we learn from historic pandemics.
Johannes Krause, Maria A. Spyrou, Michal Feldman, Alexander Herbig and Kirsten I. Bos
Max Planck Institute for the Science of Human History, Jena, Germany
Amsterdam, April 2016
Johannes Krause| Ancient Pathogen Genomics: What we learn from historic pandemics.|
Page 1
y
r
Introduction
a
r
b
i
L
e r
D ho
I
t
M
u
C
a
S
y
E
b
History of infectious Disease:
Most infectious diseases likely originated
during the Neolithic due to Zoonosis,
e.g. measles, smallpox, flu, tuberculosis,
plague, leprosy , or pertussis
Neolithic Farmer
Johannes Krause| Ancient Pathogen Genomics: What we learn from historic pandemics.|
Page 2
Carol Schauer
y
r
Introduction
a
r
b
i
L
e r
D ho
I
t
M
u
C
a
S
y
E
b
History of infectious Disease:
Most infectious diseases occurred
during the Neolithic due to Zoonosis,
e.g. measles, smallpox, flu, tuberculosis,
plague, leprosy , or pertussis
Major pandemics in history
Plague of Athens 5th century BC (measles ?)
Antonine plague 2nd century AD (smallpox?)
Justinianic plague 6th century AD (bubonic plague)
Black Death 14th century AD (bubonic plague)
White Plague (16th century TB pandemic)
Johannes Krause| Ancient Pathogen Genomics: What we learn from historic pandemics.|
Page 3
y
r
Introduction
a
r
b
i
L
e r
D ho
I
t
M
u
C
a
S
y
E
b
History of infectious Disease:
Most infectious diseases occurred
during the Neolithic due to Zoonosis,
e.g. measles, smallpox, flu, tuberculosis,
plague, leprosy , or pertussis
Major pandemics in history
Plague of Athens 4th century BC (measles ?)
Antonine plague 2nd century AD (smallpox?)
Justinianic plague 6th century AD (bubonic plague)
Black Death 14th century AD (bubonic plague)
White plague (16th century TB pandemic)
Since the 1980s we see a new wave of emerging infectious
diseases, e.g. HIV, SARS, Hanta, Ebola, Lyme disease, and
Re-emerging infectious disease with antibiotic resistance e.g. MDR-Tb
Johannes Krause| Ancient Pathogen Genomics: What we learn from historic pandemics.|
Page 4
y
r
Introduction
a
r
b
i
L
e r
D ho
I
t
M
u
C
a
S
y
E
b
Little known about : - Early evolution of pathogens
- Evolutionary rates of pathogens
- Host-pathogen interactions over time
Ancient Pathogen Genomics
-
Molecular fossil record for pathogens
Long time mutation rates
Host-pathogen interactions through time
Identify causative agents of pandemics
Johannes Krause| Ancient Pathogen Genomics: What we learn from historic pandemics.|
Page 5
y
r
Fishing for ancient pathogen genomes
a
r
b
i
L
e r
D ho
I
t
M
u
C
a
S
y
E
b
DNA capture Array
Plant
Plant
Bacteria
Fungal
Bacteria
Pathogen
Human
NGS – Sequencing
Johannes Krause| Ancient Pathogen Genomics: What we learn from historic pandemics.|
Page 6
y
r
Ancient Pathogen Genomics
a
r
b
i
L
e r
D ho
I
t
M
u
C
a
S
y
E
b
Kirsti Bos
Alexander Herbig
Verena Schuenemann
Bos et al. 2011,
Nature
Schuenemann et al. 2013,
Science
Yoshida et al. 2013,
eLife
Yersinia pestis
(bubonic plague)
Mycobacterium leprae
(leprosy)
P.infestans
(Irish potato famine)
Bos et al. 2014,
Nature
Maixner et al. 2016,
Science
M. tuberculosis
(tuberculosis)
H.pylori
(gastric ulcers)
Johannes Krause| Ancient Pathogen Genomics: What we learn from historic pandemics.|
Page 7
y
r
Bubonic plague a rodent disease
a
r
b
i
L
e r
D ho
I
t
M
u
C
a
S
y
E
b
Yersinia pestis
infected flea
bubo
8|
Johannes Krause| Ancient Pathogen Genomics: What we learn from historic pandemics.|
Page 8
y
r
The three historical plague pandemics
a
r
b
i
L
e r
D ho
I
t
M
u
C
a
S
y
E
b
• Justinianic plague (541-543) first
historically recorded in Egypt
• Black Death (1347-1353) estimated
to have killed 30-50% of Europeans
at the time
• Third Pandemic (1855-1959) started
in Yunnan province China
• genomic evidence for Yersinia pestis
as causative agent for all three
pandemics
• recently also molecular evidence for
Neolithic/Bronze age plague
epidemics
Rasmussen et al., Cell, 2015
Johannes Krause| Ancient Pathogen Genomics: What we learn from historic pandemics.|
Page 9
y
r
The second plague pandemic
a
r
b
i
L
e r
D ho
I
t
M
u
C
a
S
y
E
b
• Black Death (1347-1353)
estimated to have killed 30-50%
of Europeans at the time
• May have spread from China
through trade routes
• Plague disappeared from
Europe in the 18th century.
• 19th century pandemic
spreading from China
Johannes Krause| Ancient Pathogen Genomics: What we learn from historic pandemics.|
Bos et al., Nature, 2011
Page 10
y
r
Samples
a
r
b
i
L
e r
D ho
I
t
M
u
C
a
S
y
E
b
East Smithfield Cementary, London
London1593
Museum of London
• well reknown Plague Cementary
• used between 1348 and 1351
• excavated in 1986
• more than 500 Skeletons excavated
•20 out of 50 tested positive for Y.pestis
with classic PCR
Bos et al., Nature, 2011
Johannes Krause| Ancient Pathogen Genomics: What we learn from historic pandemics.|
Page 11
y
r
Y. pestis phylogeny
a
r
b
i
L
e r
D ho
I
t
M
u
C
a
S
y
E
b
Branch 2
Branch 1
Branch 3
19th c. pandemic
Spreading from China
Branch 4
London, 1348-50
London, 1350-1400
Marseille, 1720-22
Branch 0
Johannes Krause| Ancient Pathogen Genomics: What we learn from historic pandemics.|
Bos et al., Nature, 2011
Cui et al., PNAS, 2013
Bos et al., eLife, 2016
Page 12
y
r
Hypotheses/Questions
a
r
b
i
L
e r
D ho
I
t
M
u
C
a
S
y
E
b
14th – 18th centuries AD
Migration to Asia?
Persistence?
Multiple introductions?
Schmid et al., PNAS, 2015
Seifert et al., PLOS One, 2016
Bos et al. , eLife, 2016
Wagner et al., Lanc. Inf. Dis, 2014
Johannes Krause| Ancient Pathogen Genomics: What we learn from historic pandemics.|
Page 13
y
r
Archaeological Sites
a
r
b
i
L
e r
D ho
I
t
M
u
C
a
S
y
E
b
Saints Màrtirs Just i Pastor
Barcelona
mid 14th century
Black Death
Mass grave
18 individuals
Bolgar City
Russia
Late 14th century
Single graves
93 individuals studied
Marktplatz, Ellwangen
Germany
16th century
Post-Black Death
Mass grave
67 individuals
Johannes Krause| Ancient Pathogen Genomics: What we learn from historic pandemics.|
Page 14
y
r
Result statistics
a
r
b
i
L
e r
D ho
I
t
M
u
C
a
S
y
E
b
Table of sequencing result statistics after array capture
Site
# of preprocessed
reads
# of mapped reads
Average
coverage
% covered 3-fold
Barcelona
60,516,261
870,477
10.3
89.88%
Bolgar City
47,595,565
1,682,954
19.28
91.46%
Ellwangen
145,645,509
442,573
4.91
73.56%
Johannes Krause| Ancient Pathogen Genomics: What we learn from historic pandemics.|
Page 15
y
r
Y. pestis phylogeny
a
r
b
i
L
e r
D ho
I
t
M
u
C
a
S
y
E
b
Branch 2
Branch 1
Branch 3
19th c. pandemic
Spreading from China
Branch 4
Bos et al., Nature, 2011
Cui et al., PNAS, 2013
Bos et al., eLife, 2016
Branch 0
London, 1348-50
Barcelona, 1300-1420
London, 1350-1400
Bolgar, 1350-1400
Ellwangen, 1500-1600
Marseille, 1720-22
Johannes Krause| Ancient Pathogen Genomics: What we learn from historic pandemics.|
Page 16
Dispersal model
y
r
a
r
b
i
L
e r
D ho
I
t
M
u
C
a
S
y
E
b
Spyrou et al., in review
Johannes Krause| Ancient Pathogen Genomics: What we learn from historic pandemics.|
Page 17
y
r
Discussion
a
r
b
i
L
e r
D ho
I
t
M
u
C
a
S
y
E
b
• Palaeogenomic analysis suggest European reservoir population in post Black
Death medieval Europe (species yet unknown)
• European origin of lineage 1 in Y.pestis phylogeny
• Lineage 1 is the most comon contemporary lineage of Y. pestis and the
causative lineage of the Third pandemic
• High mobility of Y.pestis through human history despite being a rodent born
pathogen
• Mobility likely facilitated due to human acitivity (trade, migration) causing
dissemination in human comensals (e.g. black rats)
Johannes Krause| Ancient Pathogen Genomics: What we learn from historic pandemics.|
Page 18
Acknowledgements
y
r
a
r
b
i
L
e r
D ho
I
t
M
u
C
a
S
y
E
b
Rezeda I. Tukhbatova
Joanna Drath
Sacha Kacki
Julia Beltrán de Heredia
Susanne Arnold
Airat G. Sitdikov
Dominique Castex
Joachim Wahl
Ilgizar R. Gazimzyanov
Danis K. Nurgaliev
Johannes Krause| Ancient Pathogen Genomics: What we learn from historic pandemics.|
Page 19