Genetic Investigations into the Black Death

Abstract

<p>This dissertation discusses molecular analyses of dental and skeletal material from victims of the Black Death with the goal of both identifying and describing the evolutionary history of the causative agent of the pandemic. Through this work, <em>Yersinia pestis</em> DNA was successfully identified in skeletal material from a well-documented Black Death burial ground, the East Smithfield cemetery of London, England (1348 -1350). The thesis presents two major methodological advancements in the field of ancient pathogen research: 1) it describes a protocol to confirm the authenticity of ancient pathogen DNA, thus circumventing tenuous issues relating to modern contaminants, and 2) it demonstrates the applicability of DNA capture methods to isolate ancient pathogen DNA from its complex metagenomic background common to ancient DNA extracts. The dissertation is comprised of three publications. The first, submitted to the journal BMC Systems Biology, describes a computational software program for oligo design that has applications to PCR, and capture techniques such as primer extension capture (PEC) and array-based capture. The second manuscript, published in the Proceedings of the National Academy of Sciences, presents a novel capture technique for retrieval of the <em>pestis</em>-specific pPCP (9.6kb) plasmid which can be used as a simple screening tool for the presence of <em>Y. pestis</em> DNA in ancient remains, and describes a method for authenticating ancient pathogen DNA. The third paper, published in the journal Nature, presents a draft genome of <em>Yersinia pestis </em>isolated from the individuals of the East Smithfield collection, thus presenting the first ancient pathogen genome in published literature. Evolutionary changes as they relate to phylogenetic placement and the evolution of virulence are discussed within an anthropological framework.</p>