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)
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:
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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