Quantitative analysis of regulatory information distribution in a developmental locus of Drosophila

Museridze, Mariam (2025): Quantitative analysis of regulatory information distribution in a developmental locus of Drosophila. Dissertation, LMU München: Fakultät für Biologie

Abstract

The development of a multicellular organism relies on the precise spatio-temporal expression of regulatory genes, which assign cell identities and define spatial domains for future traits. This expression is controlled by enhancers—regulatory DNA sequences that determine when, where, and how much of a gene is expressed. Enhancers are traditionally described as small, modular elements that activate transcription regardless of their orientation or distance from the target promoter. This definition is largely based on qualitative assessments that focus on an enhancer’s ability to drive a specific spatial expression pattern in reporter assays. However, such an approach often overlooks DNA fragments that do not alter the spatial pattern but may still influence transcript abundance, leading to a disproportionate focus on minimal enhancer elements necessary for spatial specificity. Studying regulatory elements in a broader context and using quantitative approaches is important, as our perception of enhancers and their structure strongly influences our understanding of the mechanisms that shape the regulatory landscape and drive the evolution of morphological phenotypes. Using the regulatory locus of the yellow gene in Drosophila, this dissertation investigates how regulatory information is distributed and how spatial and quantitative aspects of gene expression are encoded in the DNA sequence. By systematically dissecting the regulatory region and employing an image registration pipeline, this study quantitatively analyzes enhancer activities responsible for gene expression in the wings and body of the fly. The findings reveal that yellow enhancers span a large genomic region, extensively overlap, and are densely packed with regulatory information. Moreover, the tested enhancers exhibit high levels of pleiotropy, challenging the conventional view of enhancer modularity. These observations have significant implications for both enhancer function and evolution.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Themengebiete: 500 Naturwissenschaften und Mathematik ; 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
• Fakultäten: Fakultät für Biologie
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 21. Juli 2025
• 1. Bericht­erstatter:in: Gompel, Nicolas