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Title: Paleovirology and the evolution of virus-host gene exchange
Author: Aswad, Amr
ISNI:       0000 0004 6497 3979
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2016
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Paleovirology is the study of viruses at large evolutionary timescales through the investigation of endogenous viral elements (EVEs) that are found in host genomes. EVEs are the result of a heritable, genomic integration of a viral genome in a host germline cell. The presence of retroviral sequences in animal genomes has been recognized since the 1970's, but discoveries made in the last five years have revealed that viruses of all genome types can endogenise. Moreover, although most EVEs are non-functional relics, there are a number of examples of functional EVEs that are co-opted to benefit the host. There remain some methodological challenges in the identification and analysis of EVEs, and we have yet to fully understand the evolutionary processes involved in the rare instances of co-option. In this thesis, I develop novel techniques to identify and characterize large herpesviruses, which lead to the discovery of the first endogenous herpesvirus in the genome of the Philippine tarsier. The same methods were redeployed to identify a new family of dsDNA virus in the genome data of their hosts. Among the 15 different new species of virus, at least four viruses in four different host fish exhibit characteristic features of EVEs such as non-sense mutations and the accumulation of transposable elements. Moreover, more than half of the predicted genes in a full-length salmon virus have no detectable similarity to known genes. The second investigative theme of this thesis explored the idea that EVEs can sometimes be the result of adaptive gene transfer, and that this is the conceptual equivalent of viral genes that are host-derived. Considering a subset of rare, functional EVEs that act as antiviral genes, I developed an evolutionary framework to understand such gene transfers as a biological strategy within the evolutionary arms race between viruses and hosts. In viruses, I conducted a systematic genome-wide evolutionary analysis of host-derived genes, which revealed a consistent shift towards higher purifying selection when switching from host to virus genome. Finally, this thesis also considered the evolution of gene transfer between viruses, by investigating the intriguing history of a retroviral superantigen gene with similarity to genes in unrelated herpesviruses. Through the evolutionary reconstruction of a large group of mammalian EVEs, I was able to prove the independent horizontal gene transfer of superantigens from retroviruses to herpesviruses from two different donor lineages. This shows that viral gene capture can occur in an evolutionary manner, and demonstrates the utility of paleovirological methods in understanding the evolution of pathogenicity. Altogether, this thesis highlights the results of synthesizing methods from paleovirology with metagenomic techniques, demonstrating that genomic databases are themselves rich with novel viral biodiversity that hold key insights for virology, genomics and evolution.
Supervisor: Katzourakis, Aris Sponsor: Poulton Scholarship ; Oxford University Zoology Department
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
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