Description
- Abstract:
- Mendelian inheritance relies on the segregation of allelic pairs during the production of gametes, allowing equal exposure of all genotypes to the forces of natural selection. There are, however, “ultra-selfish” genes that “cheat” the system by promoting their own transmission, often through destruction of the alternative allele. One example of this type of behavior is the Segregation Distorter (SD) locus in Drosophila melanogaster. This “ultra-selfish” gene acts on a target locus, known as Responder (Rsp) to destroy nuclei containing non-SD-bearing chromosomes, thus enhancing its own transmission. The Sd locus itself encodes a truncated RanGAP protein. In the cytoplasm, wild type RanGAP facilitates RanGTP hydrolysis, allowing release of cargo exported through the nuclear pore. Sd-RanGAP, a C-terminal truncation, lacks the proper localization signals and accumulates in the nucleus where it may deplete the nuclear RanGTP concentration. The Responder locus comprises an array of satellite DNA sequences. Greater repeat copy number results in higher sensitivity of that chromosome to destruction by SD. In spite of more than 50 years of study, the mechanism by which Sd-RanGAP acts on Rsp is unknown. Recently, Rsp sequences have been detected as piRNAs. These small RNA species play an essential role in ensuring faithful vertical gene transmission by silencing transposons in the germline. Additionally, other “ultra-selfish” genes indentified in D. melanogaster and D. simulans are likely regulated by this germline-specific RNA interference pathway. To evaluate the role of the piRNA pathway in segregation distortion, I tested mutations to multiple piRNA pathway components for their effects on distortion. Additionally, I used homologous recombination to specifically test the effect of mutations to the Aubergine locus on an SD chromosome. I have also examined the populations of Rsp small RNAs present in the testis and studied the localization of RanGAP and piRNA pathway components during spermatogenesis. These studies reveal that mutations in both aub and piwi act as enhancers of segregation distortion, suggesting a model whereby the normal function of the piRNA pathway acts to prevent the altered transmission ratios that characterize SD.
- Notes:
- Thesis (Ph.D. -- Brown University (2012)
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Citation
Gell, Selena L.,
"Genetic Identification of Germline RNAi Components as Regulators of Segregation Distorter in D. melanogaster"
(2012).
Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://doi.org/10.7301/Z00P0XBM
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Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations
Theses and Dissertations for the Molecular Biology, Cell Biology, and Biochemistry department....