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Functional Analysis of the Sex Related Gene dmrt1 in Xenopus

dc.contributor.advisorEvans, Ben
dc.contributor.authorKukoly, Lindsey
dc.contributor.departmentBiologyen_US
dc.date.accessioned2023-09-05T19:44:14Z
dc.date.available2023-09-05T19:44:14Z
dc.date.issued2023-11
dc.description.abstractSex determination is a key developmental process in several species regulated by sexrelated transcription factors. In many species a gene called doublesex and mab-3 related transcription factor 1 (dmrt1), plays an important role in sexual differentiation. I used African clawed frogs (Xenopus) to examine function of dmrt1 in two species: a diploid species, X. tropicalis, and an allotetraploid species, X. laevis. In both species, dmrt1 is an autosomal gene; Xenopus tropicalis has one copy of dmrt1 and X. laevis has two homeologous copies that by definition are derived from whole genome duplication: dmrt1.L and dmrt1.S in X. laevis. We generated knockouts of each of these genes to further examine their function in sexual differentiation. Histological examination showed testicular dysgenesis in X. tropicalis dmrt1 and X. laevis dmrt1.L null males whereas dmrt1.S null males presented no obvious difference in sperm density compared to wildtype males. X. tropicalis dmrt1 and X. laevis dmrt1.L null females were found to completely lack reproductive organs and are infertile whereas dmrt1.S null females appeared unaffected. The contrasting results between dmrt1.L and dmrt1.S in X. laevis provides evidence of both neofunctionalization and subfunctionalization following gene duplication and suggest that gene duplication is a major contributor to evolutionary change. Additional investigation of the transcriptome of these frogs and the role of dmrt1 in the secondary sex characteristic vocalization provides further evidence of the role of dmrt1 in development. Comprehensively, this investigation provides further knowledge of the role of dmrt1 and homeologs of this gene in sexual differentiation and introduces a novel aspect of this gene in female development. Future efforts are focused on generating double knockouts for dmrt1.L and dmrt1.S, further examining the role of dmrt1.S in somatic cell function and developing additional mutant lines in other Xenopus for comparative analysis.en_US
dc.description.degreeMaster of Science (MSc)en_US
dc.description.degreetypeThesisen_US
dc.description.layabstractIn many species sexual differentiation is a crucial developmental event. Surprisingly, however, the systems orchestrating sexual differentiation are highly variable among species. The doublesex and mab-3 related transcription factor 1 (dmrt1) gene plays a role in sexual differentiation in many groups, but its specific roles in this process are incompletely characterized and potentially diverse. We used genetic engineering in two species of African clawed frog (Xenopus) to disable function of dmrt1 in order to explore effects on gonadal development and the development of secondary sex characteristics. We found that dmrt1 is required for normal ovary or testis development in both Xenopus species, and that functional divergence occurred following duplication of dmrt1 by whole genome duplication. Taken together, these findings identify previously uncharacterized roles of dmrt1 in Xenopus and provide evidence of dynamic functional evolution of this important gene.en_US
dc.identifier.urihttp://hdl.handle.net/11375/28873
dc.language.isoenen_US
dc.subjectXenopus laevisen_US
dc.subjectXenopus tropicalisen_US
dc.subjectSex determinationen_US
dc.subjectEvolutionary geneticsen_US
dc.subjectdoublesex and mab-3 related transcription factor 1 (dmrt1)en_US
dc.titleFunctional Analysis of the Sex Related Gene dmrt1 in Xenopusen_US
dc.title.alternativeMechanistic investigation of the sex related gene dmrt1 in African clawed frogs (Xenopus) evidences both neofunctionalization and subfunctionalizationen_US
dc.typeThesisen_US

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