Studies on the Modular Evolution of Genes

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.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

National University of Ireland Maynooth

Year dc:date.issued

2019

Author dc:creator

• Leigh, Robert James

Language dc:language

en