Investigation of whether known gene expression-regulating genetic switches possess pleiotropic activities
Katherine A. Kohnen
Animals build, organize, and maintain a diversity of cell types throughout development and adulthood. Cellular diversity results from the regulated expression of genes, where most genes are “pleiotropic” with expression occurring in several cell types and/or developmental stages. Cell type and developmental stage-specific patterns of expression are switched on by cis-regulatory element (CRE) DNA sequences. In contrast to genes, CREs are generally assumed to function in a modular non-pleiotropic manner. Each CRE activates expression in one cellular context, and gene pleiotropy arises from their regulation by multiple modular CREs. This assumption shapes the way CREs are thought to impact development, evolution, and genetic disease. However, the generality of CRE modularity has not been satisfactorily demonstrated, as it is difficult to test for CRE activity or inactivity in all cell types and developmental stages. The central goal of my thesis research was to explore whether some well-studied CREs possess pleiotropic gene expression-regulating activities. Of high interest was the CRE known as the t_MSE that regulates male-specific expression of the Drosophila melanogaster tan gene as a part of a program to develop melanic cuticle plates on the posterior abdomen of this fruit fly species. In this thesis, I give an account of my studies, which did not find a pleiotropic activity for the t_MSE and which shares a cautionary tale of how experiments studying CRE function can provide false positive results. In the future, studies should explore additional CREs for pleiotropic activates to better gauge whether CRE pleiotropy is rare or common. The outcomes will have broad implications in biology, notably on the roles of CREs in development, evolution, and genetic disease.
Tom M. Williams
Primary Advisor's Department
Stander Symposium project, College of Arts and Sciences
United Nations Sustainable Development Goals
Good Health and Well-Being
"Investigation of whether known gene expression-regulating genetic switches possess pleiotropic activities" (2022). Stander Symposium Projects. 2406.