Mutations Increasing Drosophila melanogaster Life Span

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dc.contributor.advisor Trudy F C Mackay, Committee Chair en_US Magwire, Michael M en_US 2010-04-02T18:25:16Z 2010-04-02T18:25:16Z 2007-10-18 en_US
dc.identifier.other etd-07052007-015111 en_US
dc.description.abstract I have assessed longevity in a collection of 1332 co-isogenic gene-trap P-element insertion lines and determined changes in life span of each insert line relative to a corresponding control line. After a secondary screen to validate an effect on phenotype, 58 insert lines were significant for an increase in life span. Starvation resistance, chill coma recovery time and climbing activity were measured on these lines to identify pleiotropic effects. A positive correlation was found for males between life span and starvation resistance as well as between life span and chill coma recovery. Females only displayed a correlation between life span and chill coma recovery, which was negative. None of the lines indicated increased fitness for all phenotypes, indicating there may be some type of trade-off. There also appears to be a lot of pleiotropic variation depending on background and sex. Ten of the lines, all with the same parental background, were chosen for a half-diallel cross to identify epistasis between the mutants. There were substantial epistatic interactions between all ten lines. Furthermore, males and females displayed vastly different patterns of epistasis, again indicating major differences in life span regulation between the sexes. Finally, a subset of seven of the lines used in the epistatic study, in addition to the corresponding parental control, were chosen for microarray analysis to look for possible pathways and novel genes involved in increasing life span. 1,996 probe sets were significant at a false discovery rate q-value threshold of q ≤ 0.0001. Tukeys tests were carried out for these probe sets to determine how each of the seven mutant backgrounds differed compared to the control and each other. In addition, each mutant background was compared individually with the control to identify any changes in expression. Gene ontologies were determined for each of the lines to identify over-represented biological functions which would indicate possible longevity pathways. Dozens of pathways were suggested, including several novel pathways. en_US
dc.rights I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dis sertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to NC State University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. en_US
dc.subject longevity en_US
dc.title Mutations Increasing Drosophila melanogaster Life Span en_US PhD en_US dissertation en_US Genetics en_US

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