Date of Completion
Johann Peter Gogarten; Jonathan Klassen
Bioinformatics | Computational Biology | Evolution | Laboratory and Basic Science Research | Other Microbiology
Inteins are molecular parasites that have been identified in unicellular organisms from the three domains of life. The intein self-excises following translation of the host gene, and therefore incurs a fitness cost for its carrier. The symbiotic state of the intein to its host is dependent on the presence or absence of a homing endonuclease domain, which facilitates horizontal transfer of the molecule. Identification of this domain provides information on the evolutionary history of the intein, as well as patterns of horizontal gene transfer in microbial communities. I have therefore developed Hidden Markov Models (HMMs) to identify homing endonuclease domains in biological sequence data. Following validation, the HMMs were used to assign symbiotic states to inteins found in the haloarchaea. This search method expands upon previous approaches to characterizing inteins, and provides molecular evidence for the presence of homing endonuclease domains. I have also created an agent-based model for the competition between intein states in a simulated microbial population. The model incorporates spatial interactions, measured efficiencies of gene transfer, and environmental perturbations to determine the conditions under which inteins spread. These simulations determined that inteins actively spread in a population that is in stationary growth phase, while carriers are outcompeted during exponential phases of growth. My computational analysis provides a new method for assessing the symbiotic state of inteins, as well as a platform for exploring the life cycle of inteins under a variety of environmental scenarios.
Skydel, Joshua J., "Identification, Characterization, and Life Cycle of Intein-Associated Homing Endonucleases" (2016). Honors Scholar Theses. 638.