Year: 2026
Type: dissertation
Abstract: Most infectious diseases that have emerged in humans during the 20th and 21st centuries arose from animal-to-human host jumps. Despite global efforts to understand and predict host jumps, our current knowledge remains insufficient to effectively prevent and manage imminent and future emergences of infectious diseases. In this thesis, I leverage large-scale genomic datasets and apply comparative tools to investigate the evolutionary processes surrounding viral host jumps at different scales. I first explored the evolutionary correlates of viral host jumps at a systems level. In this work, I employed a taxonomy-agnostic clustering approach to partition the diversity recovered in nearly 60,000 complete viral genomes infecting 32 vertebrate families into equivalent ‘operational taxonomic units’ (OTUs). I then applied an automated phylogenetic pipeline to these OTUs to directly infer the number and types of host jumps, demonstrating that humans have given more viruses to animals than they have to us. Additionally, I find that across taxa, host jumps are generally associated with heightened evolution, though generalist viruses generally underwent fewer adaptations than specialists with narrower host ranges. I then quantified the evolutionary drivers of host jumps at a more granular taxonomic resolution, using the major wildlife pathogen ranaviruses as a case study. Here, I designed and applied a large-scale data mining pipeline to all publicly available sequencing data, enabling me to double the number of ranavirus genomes available for analysis. I then used this expanded dataset to detail the gene content and mutational adaptive signatures associated with both deep and recent host jumps of ranaviruses between fish, reptiles, and amphibians. In my final work, I demonstrated how we may pre-empt host jumps of yet-unseen viruses through metagenomics. Leveraging deep sequencing data of faecal samples collected from nearly all UK bat species, I recovered a rich diversity of coronaviruses, including two novel viral species. Working with a multi-disciplinary team of molecular and structural biologists, I then assessed the zoonotic potential of these viruses, finding that the UK bat coronaviruses we recover can infect human cells in vitro but would require additional adaptations to successfully infect humans in vivo. Taken together, this thesis sheds light on the evolutionary drivers and correlates of viral host jumps, with the potential to inform broader pandemic preparedness and mitigation efforts.
Author: Tan, Cedric CS
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7223542942