Expanding the global virome: utilising bioinformatics to discover new exogenous and endogenous viruses in vertebrates

Abstract

Viral outbreaks and zoonoses are expected to increase in incidence globally over the coming decades. Anthropomorphic-driven changes like altered climate, urbanisation and growing populations increase the interaction and proximity of animal species, providing increased opportunities for virus host switching, e.g. zoonosis, and evolution. Understanding the evolution, diversity and abundance of viruses within vertebrates is vital to prepare for future viral outbreaks and provide the tools to develop transmission mitigation strategies, rapid detection methods, treatments and vaccines to prevent global biodiversity loss. In this thesis, the overarching aim was to discover new viruses in vertebrates to understand the evolutionary history of viral families, their host ranges, genetic exchange, and the diseases they cause. For viral discovery, we developed novel bioinformatics workflows to allow high-throughput analysis of terabytes of next-generation RNA and DNA sequencing data. We focussed on historically under-studied vertebrates - amphibians, reptiles and marsupials and used a combination of metatranscriptomic and genomic data to identify both exogenous (infecting) and endogenous (fossilised) viruses in 270 RNA datasets and 19 animal genomes from 147 different species. The first chapter investigated viruses in amphibians and reptiles; key intermediate species in the early evolution of terrestrial vertebrates. We took 235 RNA datasets from 122 species and identified 26 novel DNA and RNA viruses from 15 viral families, highlighting the unsampled diversity of viruses circulating in these wild animals. In the second and third chapters we studied Australian marsupials; early mammals that have evolved in geographical isolation for hundreds of millions of years. We screened 35 RNA datasets and 19 genomes and identified over 80,000 endogenous virus fragments, primarily from Retroviridae. We identified both exogenous and endogenous viruses to better understand the unique Australian virome that has established through marsupial coevolution, and their impact on the animals they have infected. We provide evidence for the extensive invasion of endogenous retroviruses throughout Dasyuridae marsupials which may contribute to genomic instability and their increased rates of cancer. It is estimated that only <0.0005% of global viral diversity has so far been characterised. This thesis identified new viruses and addressed gaps in our knowledge of vertebrate virus evolution