The evolutionary history of plague as revealed through the analysis of ancient Yersinia pestis genomes

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URI: http://hdl.handle.net/10900/84300
http://nbn-resolving.de/urn:nbn:de:bsz:21-dspace-843003
http://dx.doi.org/10.15496/publikation-25690
Dokumentart: Dissertation
Date: 2020-09-11
Language: English
Faculty: 7 Mathematisch-Naturwissenschaftliche Fakultät
Department: Geographie, Geoökologie, Geowissenschaft
Advisor: Krause, Johannes (Prof. Dr.)
Day of Oral Examination: 2018-08-03
DDC Classifikation: 500 - Natural sciences and mathematics
570 - Life sciences; biology
930 - History of ancient world to ca. 499
Keywords: DNS , Mikrobiologie , Archäologie , Genomik
Other Keywords:
ancient DNA
ancient pathogen genomics
bacteria
plague
License: Publishing license including print on demand
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Inhaltszusammenfassung:

Dissertation ist gesperrt bis 11. September 2020 !

Abstract:

The study of ancient pathogen genomics has the potential to reveal key insights into the history of infectious disease as well as into the processes that have triggered pathogen emergence leading to epidemics/pandemics. A characteristic historical example of abrupt infectious disease emergence is that of plague during the Black Death (1346- 1353 AD), which claimed the lives of up to 60% of the European population in only five years. In the present thesis, I have investigated the genetic history of its causative agent, Yersinia pestis, by tracing back some of the earliest phases of its evolution, but also by studying its infamous, and historically documented, medieval epidemics. This work has been possible through the adoption of both in vitro and in silico methodologies for the detection of Y. pestis DNA in ancient human remains as well as for its enrichment, NGS sequencing and genome reconstruction. One of the sections of this thesis reveals key insights into the origin of flea-mediated transmission in Y. pestis, which is known to lead to the typical disease presentation referred to as bubonic plague. Contrary to previous research suggesting that during its early evolution Y. pestis was unable to transmit via the flea vector, I describe strains from ~4,000 years ago that show genetic compatibility with this mode of transmission. This traces the origins of bubonic plague back to the Bronze Age and shows the parallel existence of several bacterial forms that had different transmission and disease potentials. After the Bronze Age, bubonic plague was the main culprit of two historical pandemics (6th – 8th and 14th – 18th centuries AD). In this thesis, I have performed genetic screening of human remains from both of these periods in order to assess the presence of Y. pestis. As a result, I am able to present a systematic study of the Black Death and its ensuing medieval plague outbreaks that occurred in Europe until the 18th-century by achieving a five-fold increase in the available genomic data that exist from that time. These data reveal a low genetic diversity in the bacterium during the Black Death, and support a link between this first wave and modern-day plague occurrences around the world. Moreover, the genomes reconstructed from later European epidemics suggest that Y. pestis persisted locally for 400-years after the Black Death, where it further diversified into multiple genetically distinct clades. These clades differ in their evolutionary rates and virulence profiles and seem to have no identified modern descendants. Finally, apart from Y. pestis genomes, this thesis also describes the analysis of human DNA from part of the studied individuals, most of which derive from epidemic contexts. Analysis of mitochondrial and nuclear DNA from Bronze Age and early medieval individuals suggests that human mobility during historic and prehistoric times may have facilitated the spread of pathogens, such as Y. pestis, across Eurasia.

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