This is a proposal to study the mechanism and evolution of the extensive RNA editing in mitochondrial genes in slime molds and the intriguing DNA rearrangement that occurs in ciliates when the somatic macronucleus is formed from the germline micronucleus. Mathematical models that would describe the RNA editing and the DNA rearrangement processes in these organisms will also be investigated. This research project consists of three parts. The first part is concerned with the reconstruction of the evolution of the RNA editing of mitochondrial genes in slime molds and the DNA rearrangement systems in ciliates using a phylogenetic approach. For this purpose, the P.I. intends to construct a reliable phylogenetic tree for different groups of species of slime molds and ciliates using ribosomal RNA sequences and then infer the evolution of four different types of RNA editing and various types of DNA rearrangements in the history of slime molds and ciliates using the parsimony method. Dr. David Prescott has agreed to collaborate in this project. The second part of the research is an experimental study to understand the molecular mechanisms of DNA rearrangement in Stylonychia lemnae. It is now known that some germline genes are composed of intervening non-coding DNA sequences (internally eliminated sequences; IESs) and macronuclear destined sequences (MDSs) and that in the process of formation of the macronucleus IES's are eliminated and MDSs are combined in a strange order to form functional genes. However, it is unknown how MDSs are rearranged in the order which is different from the original order of MDSs in the germline gene. The P.I. plans to study the mechanisms of DNA rearrangement through a series of functional experiments involving DNA transformation, genetic analysis, and PCR analysis of the time-course of rearrangement to test specific aspects of different models of rearrangements. This part of the work will be done in the laboratory of Dr. Hans Lipps in Germany. The third part of the research project is concerned with the mathematical modeling of RNA editing and DNA rearrangement. It is stated that the DNA rearrangement process is similar to a directed Hamiltonian path problem in mathematics and that the rearrangement is mathematically very efficient. The P.I. now wants to develop a better mathematical theory for describing this process. This part of the work will be done in collaboration with Dr. L. Kari (University of Western Ontario) and Dr. G. Rozenberg (Leiden University).
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