Research proposal: Evolution of the Dorsal-Ventral gene regulatory network in Drosophila species

Gene regulation in animals is arguably at least as important as the genes that are being regulated. Animal body plans, their structures and in particular the functions that the animal morphology provides, are the consequence over time and space of successive regulatory and developmental processes. Gene regulation in animals is a highly complex process, and can be likened to a computation that the regulatory machinery performs. Often, single genes are regulated by a complex network of genes with activators, repressors, attenuators and the like, and the elucidation of these networks has taken molecular and develop- mental biologists decades. But while we know a tremendous amount about how genes and their associated proteins evolve, much less is known about how regulatory systems evolve. We know the basic building blocks: multiple transcription factor binding sites that regulate the expression of other transcription factors that ultimately lead to the expression of the regulated gene. Each transcription factor has a specific affinity to its binding site, and binding sites can interact either synergistically or antagonistically. If we compare the regulatory regions for the same gene across species in the same family, we can see sometimes significant differences in the regulatory sequence. Are these differences adaptive? How do regulatory networks change in response to changes, either in the environment or in response to a change in body size? In the proposed work, we will analyze the gene regulatory network or “cis-regulatory module” (CRM) that regulates the patterning of a fly embryo in the dorsal-ventral axis. This is a well-studied system for which expression and sequence data is available from the Arnosti lab, and aligned homologous CRMs have been collected. Yet, we do not know in detail how evolution affects such systems. What are the “operators” that evolution uses to change these networks? A computational analysis of the regulatory region of 12 Drosophila species will help us move towards a better understanding of how regulatory systems evolve.