Dr Jonathan Pettitt (University of Aberdeen) https://www.aberdeenwormlab.org/
Dr Berndt Mueller (University of Aberdeen) https://www.aberdeenwormlab.org/
Dr Marius Wenzel (University of Aberdeen) https://www.abdn.ac.uk/people/marius.wenzel
Professor Ian Stansfield (University of Aberdeen) https://www.abdn.ac.uk/people/i.stansfield
An emerging challenge in evolutionary biology is to understand the phenomenon of recurrent genomic evolution, defined as the independent emergence of the same molecular process in multiple taxa. Recurrent genomic evolution is important because it implies that there are biases built into living systems, which can tell us about the structure of these systems and the mutational paths that are available for the evolution of specific traits.
An intriguing example of such a recurrent genomic evolution is eukaryotic polycistronic RNA processing - a mechanism that has independently evolved many times in different eukaryotic taxa. To carry out this process, two highly conserved, fundamental eukaryotic gene expression mechanisms, mRNA 3’ processing/polyadenylation and the spliceosome, must be modified without impairing their ancestral functions. Thus, there are clear constraints on how polycistronic RNA processing can evolve, but there is also evidence that there are multiple pathways to evolving this trait.
This project will involve comparative computational biology of genomes and transcriptomes from a broad range of eukaryotes to investigate the constrained and variable elements of polycistronic RNA processing. The student will develop analysis pipelines in a Linux and R-based environment with a focus on processing high-throughput sequence data, genome assembly, genome annotation and statistical comparative genomics. Pilot data that validated this approach in nematode species is available and full training will be provided for all computational approaches.
In parallel to this, we will investigate the rules underlying the evolution of polycistronic RNA processing using a yeast-based system. We will use forced evolution in the laboratory to select for increases in the efficiency of polycistronic RNA processing, exploiting synthetic biology approaches in a yeast strain expressing nematode RNA factors that we have developed to specifically study this problem. This will allow us to identify the changes that occur during the emergence of polycistronic RNA processing and complement our studies of organisms in which this process is already well established.
The study of polycistronic RNA processing across the Eukarya offers a unique opportunity to investigate the constraints that operate during the diversification of a conserved molecular process. Many of the eukaryote groups that use polycistronic processing as an essential gene expression strategy contain important human, animal and plant pathogens. Thus, these studies will also highlight potential avenues for the development of novel therapeutic interventions to treat parasitic infections.
Application Procedure: http://www.eastscotbiodtp.ac.uk/how-apply-0
Please send your completed EASTBIO application form, along with academic transcripts and CV to Alison McLeod at [email protected]
. Two references should be provided by the deadline using the EASTBIO reference form. Please advise your referees to return the reference form to [email protected]
Maeso I, Roy SW, Irimia M. Widespread recurrent evolution of genomic features. Genome Biol Evol. 2012;4: 486–500.
Wenzel MA, Johnston C, Müller B, Pettitt J, Connolly B. Deep evolutionary origin of nematode SL2 trans-splicing revealed by genome-wide analysis of the Trichinella spiralis transcriptome [Internet]. bioRxiv. 2019. p. 642082. doi:10.1101/642082