Next generation sequencing to explore microbial diversity, origins and evolution

Abstract

Emerging infectious diseases are major contributors to morbidity and mortality. To prevent such diseases from occurring in the future it is important to understand pathogen evolution and emergence. Unfortunately, we know little about the virosphere outside of clinically significant viruses, leaving the bulk of viral diversity unexplored. A key aim of my thesis was to reveal more of the unknown diversity of viruses, particularly in under-studied animal hosts. To this end I employed bulk RNA sequencing (“meta-transcriptomics”) to identify novel viruses in a range of hosts, including native Australian wildlife and invertebrate species, as well as from mining databases of short-read archives. The novel viruses discovered were associated with an array of viral families, including the Flaviviridae, Parvoviridae, Circoviridae, Nudiviridae, Polyomaviridae, and Herpesviridae, in turn expanding our knowledge of the diversity and evolutionary history of these families. I similarly used meta-transcriptomics to document the presence of viral, bacterial and eukaryotic parasite sequences in commonly used laboratory reagents. Additionally, I explored the evolutionary history of two important members of the family Poxviridae: variola virus and the vaccinia virus. Accordingly, I described the historical context of smallpox, with an emphasis on the initial outbreak in Australia, and used ancient DNA techniques to reveal the origins and evolutionary history of the poxviruses used in early vaccination campaigns. Broadly, this thesis has expanded our knowledge of the diversity of viruses and revealed the evolutionary history of viral families that have a major impact on human and animal health. By increasing our knowledge of viral diversity, my work provides important new insights into their ecology and evolution, particularly the transmission of viruses to new host species that underpins disease emergence.