Leigh, Robert James (2019) Studies on the Modular Evolution of Genes. PhD thesis, National University of Ireland Maynooth.
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Abstract
Gene evolution is primarily studied through the observations of comparative
cumulative point mutations between homologs. Genes also evolve through “remodelling”, the
process of repurposing and reorganising genes and gene fragments into novel sequences. Gene
remodelling is a relatively underappreciated evolutionary concept. Remodelling events
circumscribe the development of novel sequences via fusion or fission events and through the
shuffling of exons or domains. To date, all studies into remodelling have focussed on specific
remodelling events, for example gene fusions in cancer samples, or have used small datasets
(<15 species). As such, a comparative remodelling analyses between two taxonomic Kingdoms
has yet to be completed. In 2018, CompositeSearch was developed to overcome the
computational bottlenecks associated with mining all possible combinations that may attribute
to remodelling events. We used CompositeSearch to investigate the comparative extent of
remodelling within large fungal (107 species) and plant (50 species) datasets. We observed
approximately 50% of fungal genes and 61% of plant genes to have a history of remodelling
despite robust controls against Type I errors. We observed the rate of remodelled family birth
and decay to be clocklike in both datasets, and that remodelled genes were considerably more
homoplastic than non-remodelled genes. Functional overrepresentation analysis concluded that
remodelled genes were associated with rapidly evolving systems, such as secondary
metabolism, and with phenotypic novelty, such as flowering in angiosperms.
Remodelling events have been associated with the development of antimicrobial
resistance (AMR). As CompositeSearch does not discern between a fusion event and any other
remodelling event, we developed CompositeBLAST to detect novel AMR fusion events.
CompositeBLAST was considerably faster and more sensitive than previously published
fusion detection tools. Using this software, we detected previously unreported mupirocin and
vancomycin resistance genes as being derived from remodelling events.
Item Type: | Thesis (PhD) |
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Keywords: | Modular Evolution; Genes; |
Academic Unit: | Faculty of Science and Engineering > Biology |
Item ID: | 12553 |
Depositing User: | Dr Robert Leigh |
Date Deposited: | 09 Mar 2020 17:07 |
URI: | https://mural.maynoothuniversity.ie/id/eprint/12553 |
Use Licence: | This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here |
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