Theses and Dissertations at Montana State University (MSU)
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Item String analysis and algorithms with genomic applications(Montana State University - Bozeman, College of Engineering, 2024) Liyana Ralalage, Adiesha Lakshan Liyanage; Chairperson, Graduate Committee: Binhai ZhuIn biology, genome rearrangements are mutations that change the gene content of a genome or the arrangement of the genes on a genome. Understanding how genome rearrangements occur in a genome can help us to understand the evolutionary history of extant species, improve genetic engineering, and understand the basis of genetic diseases. In this dissertation, we explored four problems related to genome partitioning and tandem duplication and deletion rearrangement operations. Our interest was focused on determining how difficult it is to solve these problems and identifying efficient algorithms to solve them. The proposed problems were formulated as string problems and then analyzed using complexity theory. In the first chapter, we explored several variations of F -strip recovery problem called XSR-F and GSR-F and their complexity under different parameters. We proved that the XSR-F problem is hard to solve unless we restrict the allowed block sizes to one size. We provided a polynomial time algorithm for GSR-F under a fixed alphabet and fixed F . In the second and third chapters, we introduced two string problems named longest letter- duplicated subsequence (LLDS) and longest subsequence-repeated subsequence (LSRS)-- formulated as alternative problem formulations for the tandem-duplication distance problem that allow to extract information about segments of genes that may have undergone tandem duplication-- analyzed the complexity of their variations and devised efficient algorithms to solve them. We proved that constrained versions of LLDS and LSRS problems are NP- hard for parameter d > or = 4, while general versions were polynomially solvable which hints that any variations closer to the original tandem duplication distance problem are still hard to solve. In the final chapter, we delved into two heuristic algorithms designed to compute genomic distance between two mitochondrial genomes and a heuristic algorithm to predict ancestral gene order under the TDRL (tandem-duplication random loss) model. We improved the previously studied method developed for permutation strings by tweaking heuristic choices aimed at calculating the minimum distance between two genomes to apply to non-permutation strings. These heuristic algorithms were implemented and tested on a real-world mitochondrial genome data set.Item Protein-Protein interactions involved in the biogenesis of eukaryotic small ribosomal subunits(Montana State University - Bozeman, College of Letters & Science, 2008) Castle, Cathy Lynn; Chairperson, Graduate Committee: Mensur DlakicRibosome biogenesis is a complicated process involving numerous proteins and modification factors. The process has been well-documented in prokaryotic cells where it is much less complex than the process involved in eukaryotic cells. In eukaryotes, much of what is known about ribosome biogenesis has been learned from studies in the yeast Saccharomyces cerevisiae. Far less has been learned about higher eukaryotes such as humans. However, among organisms in all three domains of life, ribosome structure and function is well conserved. The biogenesis of ribosomal subunits is dynamic, complicated, and, in S. cerevisiae, requires over 200 trans-acting factors for synthesis to occur. The focus of this study is synthesis of the small ribosome subunit in eukaryotes. In order to study this process in higher eukaryotes, a mammalian cell culture method was used. This method involves cloning human ribosomal accessory genes using the Gateway system, a rapid and efficient cloning method that permits parallel construction of numerous plasmids in a modular type of system, each containing the desired gene of interest in a variety of vectors. Proteins were selected based on their activity in yeast with emphasis on the final processing step of the small subunit and the proteins that are involved at that step. These proteins are Nob1p, Enp1p, Tsr1p, Rio2p, Rrp20p, Dim1p, and Hrr25p. The corresponding genes were cloned into vectors containing either the coding region for a full-length fluorescent protein or the C-terminus or N-terminus half of the fluorescent protein. The bimolecular fluorescent complementation assay (BiFC) was then utilized to detect protein-protein interactions. Results of this assay demonstrate binary interactions among pairs of this group of proteins and the location within the cell where these interactions take place.