Fig 4. Conceptual model of transcriptional regulatory network evolution under the influence of genome reduction.

For this model we used the classification proposed by N. Moran [18]. We start with a standard regulatory network (composed by activators, repressors, and dual regulators) corresponding to a free-living organism, in this case E. coli. In the first (early) stage of genome reduction, organisms are recently host-restricted symbionts or pathogens. These organisms have lost different TFs and TGs; however, the whole process of transcriptional regulation is similar to that of free-living organisms. In the second (advanced) stage of genome reduction, organisms turn into obligate symbionts or pathogens. In this stage, the majority of TFs in the TRN has been lost. We surmise that, in these bacteria, transcriptional regulation is exerted mainly at the structural level of DNA. In the last (extreme) stage, organisms exhibit extreme genome reduction and they no longer conserve TFs. Examples of organisms in each group are included, as well as the conserved parental classes of their gene-products according to the gene ontology classification.