The in silico identification and analysis of ancient and recent endogenous retroviruses in mammalian genomes
File(s)
Author(s)
Lee, Adam
Type
Thesis
Abstract
Recent advances in DNA sequencing technologies have led to a vast plethora of vertebrate genomes being made available for bioinformatic analysis and investigation. This has presented retrovirologists with many new opportunities to study endogenous retroviruses (ERVs) – selfish genetic element (SGEs) endogenised within the genomic DNA of their hosts. Many of these ERVs exist as molecular fossils of past germline infections by their exogenous counterparts, representing approximately 8-10% of mammalian genomes. While the majority are thought to be inactive today, one particular retroviral group – HERV-K(HML-2) – has been implicated in recent activity. In this thesis, efficient, synergistic in silico techniques have been implemented, with which intensive, genome-wide retroviral screens were performed. This has culminated in the identification of 11 novel, insertionally polymorphic human ERVs (HERVs), belonging to the HERV-K(HML-2) lineage, in two high- coverage archaic hominid genomes. This thesis also identifies the oldest ERV described to date – orthologous across all placental mammals – estimated to have endogenised in the germline of an ancestral mammal, 128-140 million years ago. Three SGEs, found to be endogenised within this ancient ERV, have also been described and assigned a minimum age of 104 million years, making these the oldest, definitively dated SGEs. This thesis also presents a computer program for renaming all identified ERVs in vertebrate genomes, according to a newly designed nomenclature standard to be implemented globally, that aims to unambiguously catalogue all the ERVs identified, to date.
Version
Open Access
Date Issued
2014-11
Date Awarded
2015-03
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Tristem, Michael
Publisher Department
Life Sciences
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)