Research highlight by Kazuharu Arakawa and Masaru Tomita, Institute for Advanced Biosciences, Keio University, Japan
Gene duplications and mutations are central driving forces in the evolution of genomes. Genomes must be robust to such changes in order to be evolvable, and many studies have probed genome robustness using systematic gene knockouts or overexpression experiments. In a recent paper, Isalan et al. (2008) took a new approach to test the robustness of Escherichia coli gene circuitry by reconstructing gene duplication events by shuffling the promoter-ORF pairs for about 300 transcription factors and introducing 598 recombined pairs one-by-one into E. coli to rewire its transcriptional network. Surprisingly, ~95% of such additions are robustly tolerated, and some networks even exhibit greater fitness under various selection pressures. Moreover, the study shows that, in contrast to naive expectations, the introduction of positive or negative feedback loops has little effect on the protein expression levels of regulated ORFs.
Since radical rewiring of the gene circuitry appears to have only a limited impact on expression levels, this work suggests that gene regulatory networks are highly dynamic and underscores the potential importance of post-transcriptional mechanisms for the robustness of transcriptional regulation. Moreover, this work illustrates the fundamental robustness and evolvability of gene regulatory networks, which is reassuring news for synthetic biology.
Isalan M, Lemerle C, Michalodimitrakis K, Horn C, Beltrao P, Raineri E, Garriga-Canut M, Serrano L (2008) Evolvability and hierarchy in rewired bacterial gene networks. Nature 452:840