Master of Science (MSc)
Faculty of Science
In prokaryotes, transcriptional regulation commonly involves a transcription factor (TF) binding to a particular conserved sequence of nucleotides (operator). Binding elicits a transcriptional response, either activation or repression. The evolution of gene regulation has been identified as a primary driver of species diversity, making it an important area of research. This work examined the dynamics of the interactions between TFs and operators, and TFs and their primary target genes in attempt to assess the rapid evolution of transcriptional regulatory networks (TRNs) across a diverse set of prokaryotes. Using software packages, operator sequences from Escherichia coli K12 were compared to every bacterial and archaeal genome within the NCBI’s RefSeq database. This revealed that, based on genome composition, native TFs have a greater probability of interacting with sequences within their host’s genome than those of other species, indicating that appropriate operators may form spontaneously, and often, within a genome. TFs and target genes were assessed through co-occurrence patterns. Recently, research has shown that repeated co- occurrence of two genes is evidence for a functional interaction. Co-occurrence can be observed and quantified in phylogenetic profiles by measuring mutual information (MI); this is a metric of how often two genes co-occur adjusted for what is expected by chance. By measuring MI for all two-gene combinations from a subset of genomes from NCBI’s RefSeq database, results showed that, in > 97% of the organisms observed, TFs form looser functional interactions than other genes, indicating that TFs do not form lasting associations on the evolutionary time scale. These results suggest regulatory interactions are not as specific or conserved as those between most other gene products. Together, these results suggest that TRNs evolve rapidly across most, if not all prokaryotes.
del Grande, Marc, "THE EVOLUTIONARY DYNAMICS OF TRANSCRIPTION FACTORS, OPERATORS, AND THEIR TARGET GENES ACROSS PROKARYOTES" (2014). Theses and Dissertations (Comprehensive). 1627.