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Master of Science
Department or Program
Department or Program Chair
Kiowa Bower, Ph.D.
Julie K. Andersen, PhD
Gordon J. Lithgow, PhD
Parkinson’s disease (PD) is largely an idiopathic disease that includes contributions from both genetic and environmental factors, with aging itself being the largest risk factor. These combined susceptibility factors are believed to accumulatively contribute to initiation and progression of Parkinson’s disease. Although most cases of PD are idiopathic, rare genetic forms of the disease do exist. In these cases, an important unanswered question is why mutations that cause the disease have come to be maintained within the human population? One possibility is based on what is known as the Antagonist Pleiotropic Theory (APT) of Aging, a theory that states that genes that confer reproductive benefit early in life may result in detrimental effects with post-reproductive aging. Mutations in the PARKIN gene are associated with PD in humans. We have made a series of observations in the model organism Caenorhabditis elegans in which, the worms carrying a mutation of the homozygous gene, pdr-1, displayed increased reproductive fitness. This suggests that familial parkin mutation may have a beneficial effect in terms of natural selection even though its known clinical effect in PD patients bearing this mutation is detrimental. This data provides the first clues as to why this particular PD-related mutation may be maintained within the population. I have investigated the mechanism of this newly identified phenotype and if environmental factors alter this affect. Specifically, we have asked whether increased fitness may be due to enhanced mitochondrial function during reproduction. Additionally, we contemplate if the environmental factor manganese (Mn), which has been identified as a risk factor for the disease, alters reproductive fitness in relation to this gene mutation.
Barhydt, Tracy Ann, "Mutations in PARKIN (pdr-1) Results in Increased Reproductive Fitness in C. elegans" (2013). Master's Theses and Capstone Projects. 62.