Application of Bioinformatics to Protein Domain, Protein Network, and Whole Genome Studies.

Bioinformatics primarily focuses on the study of sequence data. Analyzing both nucleotide and protein sequence data provides valuable insight into their function, evolution, and importance in organism adaptation. For this dissertation, I have applied bioinformatics to the study sequence data on three levels of complexity: protein domain, protein network, and whole genome.

In the protein domain study, I used sequence similarity searches to identify a novel FIST (F-box and intracellular signal transduction proteins) domain. The domain was found to exist in all three kingdoms of life, pointing to its functional importance. Due to its presence exclusively with transducer and output domains, it was deduced that FIST functions as an input/sensory domain involved in signal transduction. Further functional characterization revealed FIST's proximity to amino acid metabolism and transport genes. This suggested that FIST functions as a small ligand sensor.

In the protein network study, I examined the evolution of the chemotaxis system within the clade of Escherichia. Our study confirmed previous results demonstrating that many urinary pathogenic Escherichia coli have lost two of their five chemotaxis receptors. However, sequence analysis demonstrates that this loss occurred as an ancestral event and was not a result of adaptive evolution. The retention of the core of the system in the vast majority of Escherichia confirms that chemotaxis is important for survival in all of Escherichia's habitats. However analysis of the loss and gain of chemotaxis receptors suggests that the array of compounds that Escherichia needs to sense often does not require all 5 canonical receptors.

In the genome study, I used comparative genomic analysis to examine the evolutionary history of Azospirillum, agriculturally important plant growth-promoting bacteria. Taxonomic and genomic studies have revealed that Azospirillum are very distinct from their closest relatives in both habitat and genome structure. Comparative genomic analysis revealed that Azospirillum had undergone massive horizontal gene transfer. Among acquired genes were many of those implicated in survival in the rhizosphere and in plant growth-promotion. It is proposed that this bacteria's unique genome plasticity and ability to uptake large amounts of foreign DNA allowed azospirilla to transition from an aquatic to terrestrial environment.