Reconstruction of the Core and Extended Regulons of Global Transcription Factors

The processes underlying the evolution of regulatory networks are unclear. To address this question, we used a comparative genomics approach that takes advantage of the large number of sequenced bacterial genomes to predict conserved and variable members of transcriptional regulatory networks across phylogenetically related organisms. Specifically, we developed a computational method to predict the conserved regulons of transcription factors across α-proteobacteria. We focused on the CRP/FNR super-family of transcription factors because it contains several well-characterized members, such as FNR, FixK, and DNR. While FNR, FixK, and DNR are each proposed to regulate different aspects of anaerobic metabolism, they are predicted to recognize very similar DNA target sequences, and they occur in various combinations among individual α-proteobacterial species. In this study, the composition of the respective FNR, FixK, or DNR conserved regulons across 87 α-proteobacterial species was predicted by comparing the phylogenetic profiles of the regulators with the profiles of putative target genes. The utility of our predictions was evaluated by experimentally characterizing the FnrL regulon (a FNR-type regulator) in the α-proteobacterium Rhodobacter sphaeroides. Our results show that this approach correctly predicted many regulon members, provided new insights into the biological functions of the respective regulons for these regulators, and suggested models for the evolution of the corresponding transcriptional networks. Our findings also predict that, at least for the FNR-type regulators, there is a core set of target genes conserved across many species. In addition, the members of the so-called extended regulons for the FNR-type regulators vary even among closely related species, possibly reflecting species-specific adaptation to environmental and other factors. The comparative genomics approach we developed is readily applicable to other regulatory networks

Tripartite ATP-independent periplasmic transporters: application of a relational database for genome-wide analysis of transporter gene frequency and organization

Tripartite ATP-independent periplasmic (TRAP) transporters are a family of extracytoplasmic solute receptor-dependent secondary transporters that are widespread in the prokaryotic world but which have not been extensively studied. Here, we present results of a genome-wide analysis of TRAP sequences and genome organization from application of TRAPDb, a relational database created for the collection, curation and analysis of TRAP sequences. This has revealed a specific enrichment in the number of TRAP transporters in several bacteria which is consistent with increased use of TRAP transporters in saline environments. Additionally, we report a number of new organizations of TRAP transporter genes and proteins which suggest the recruitment of TRAP transporter components for use in other biological contexts

The Design Improvement Controlled Experiment (DICE) An evaluation of the impact, costs and benefits of estate re-modelling

Work carried out by Price WaterhouseAvailable from British Library Document Supply Centre-DSC:GPE/0683 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo