Revealing the evolution of viruses using phylogenetics, metagenomics and structural prediction

Abstract

Metagenomic sequencing, particularly total RNA sequencing (i.e., meta-transcriptomics), has emerged as a powerful tool for virus discovery. Although the known virosphere has expanded dramatically in recent years, the viruses associated with much of the tree of life remain largely undiscovered, limiting our ability to infer the evolutionary and ecological processes that shape viral diversity. The central aim of my thesis was to explore viral diversity in under-sampled species critical to answering fundamental questions about virus evolution and ecology. To achieve this, I combined metatranscriptomic sequence data with state-of-the-art phylogenetic and structural analysis. I determined a novel papillomavirus, a likely aetiological agent of oral papilloma-like lesions in a fur seal, and characterised the virome of Australian dogs, including the first RNA virus in dingoes. I also conducted broad virus discovery surveys of publicly available transcriptome data sets. By analysing species from across the breadth of the plant kingdom I identified 104 potentially novel viruses, including sequences divergent enough to represent novel virus families, as well as the first virus genomes in bryophytes and lycophytes. Through an analysis of flaviviruses across the Metazoa I discovered 32 novel flavivirus sequences. These included an orthoflavi-like virus in a coral, marking the earliest diverging metazoan host, and a substantial expansion of the host range of pestiviruses. I next used the expanded Flaviviridae sequence data set to investigate glycoprotein distribution within the family. Through structural homology searches I uncovered a complex evolutionary history for the Flaviviridae, characterised by bacterial gene capture and inter-genus recombination. In sum, the research in this thesis expands the known virosphere and highlights how novel and highly divergent viruses can be key to uncovering the fundamental mechanisms, patterns, and processes of virus evolution.