Sarah Teichmann MRC Laboratory of Molecular Biology, Cambridge, England Evolution and Dynamics of Transcriptional Regulatory Networks The biological characteristics of an organism emerge, in large part, as a result of the dynamic inter-play between its gene repertoire and the regulatory apparatus, which includes transcription factors and signal transducers. We have analyzed the possible evolutionary histories and the dynamics of transcriptional regulatory systems from a network perspective (Teichmann & Babu, 2004). For the transcriptional regulatory network of the prokaryote E. coli and the unicellular eukaryote S. cerevisiae, we have defined possible duplication scenarios for generating new regulatory interactions between transcription factors and target genes. We show that over one third of the regulatory interactions have evolved by duplication of transcription factors and target genes followed by inheritance of interactions from the ancestral gene. This mechanism is not primarily responsible for the overall network topology or specific topologies of network motifs. Next we turn to network evolution across prokaryotes based on the E. coli transcriptional regulatory network as a template, and ask whether regulatory interactionsare conserved between organisms. Target genes tend to be more conserved than transcription factors, and there is no bias for conservation of network motifs. The transcriptional regulatory network has changed in evolution, and it also changes within an organism depending on the external and internal conditions of the cell. We have studied the dynamics of the transcriptional regulatory network in Saccharomyces cerevisiae on a genomic scale, by integrating regulatory information and gene-expression data for multiple conditions (Luscombe et al., 2004). Contrary to expectation, we uncover large changes in underlying network architecture between different states. A few TFs serve as permanent hubs while most act transiently during particular conditions. Looking at sub-network structures, we show environmental responses facilitate fast signal propagation (eg with short regulatory cascades), whereas the cell cycle and sporulation direct temporal progression through multiple stages (eg with dense TF inter-regulation). With these studies, we are shedding light on the ways in which network topology is shaped by evolutionary mechanisms and cellular conditions. Teichmann, S.A. & Babu, M.M. (2004) Gene Regulatory Network Growth by Duplication. Nature Genet., 36, 492-496. Luscombe, N.M., Babu, M.M., Yu, H., Snyder, M., Teichmann, S.A. & Gerstein, M. (2004) Genome-scale analysis of regulatory network dynamics. Nature, 431, 308-312. Time: 9 March 2005 Place: 8.01 EC Stoner, Boardroom, School of Computing. Back to seminar list