Bacterial regulatory networks are extremely flexible in evolution

Abstract

Over millions of years the structure and complexity of the transcriptional regulatory network (TRN) in bacteria has changed, reorganized and enabled them to adapt to almost every environmental niche on earth. In order to understand the plasticity of TRNs in bacteria, we studied the conservation of currently known TRNs of the two model organisms Escherichia coli K12 and Bacillus subtilis across complete genomes including Bacteria, Archaea and Eukarya at three different levels: individual components of the TRN, pairs of interactions and regulons. We found that transcription factors (TFs) evolve much faster than the target genes (TGs) across phyla. We show that global regulators are poorly conserved across the phylogenetic spectrum and hence TFs could be the major players responsible for the plasticity and evolvability of the TRNs. We also found that there is only a small fraction of significantly conserved transcriptional regulatory interactions among different phyla of bacteria and that there is no constraint on the elements of the interaction to co-evolve. Finally our results suggest that majority of the regulons in bacteria are rapidly lost implying a high-order flexibility in the TRNs. We hypothesize that during the divergence of bacteria certain essential cellular processes like the synthesis of arginine, biotine and ribose, transport of amino acids and iron, availability of phosphate, replication process and the SOS response are well conserved in evolution. From our comparative analysis, it is possible to infer that transcriptional regulation is more flexible than the genetic component of the organisms and its complexity and structure plays an important role in the phenotypic adaptation.

Figure 1

Conservation of the components of the TRN (TFs and TGs) across the three domains of life for (a) E.coli K12 and (b) B.subtilis. In X-axis are 110 non-redundant genomes ordered by phylogenetic distance (Materials and Methods). In Y-axis (to the left) is the percentage of conservation of the elements (TFs and TGs) of the TRNs. CI values (shown to the right on the Y-axis) represent a measure of conservation of the components of the TRN of a genome with respect to the conservation of its genes. Color codes on X-axis represent different phylogenetic clades as described in Supplementary Data.

Figure 2

Conservation of GRs and their regulons across genomes for (a) E.coli K12 and (b) B.subtilis. Note that for GRs only presence (in black) or absence (in white) is shown (upper section) while for regulons percentage of interactions conserved is shown (lower section for each GR). Genomes are arranged in increasing order of phylogenetic distance with respect to the organism of reference.

Figure 3

Classification of TF–TG pairs into three different categories. Examples of TF–TG pairs distributed in to different classes based on their co-evolution pattern: (a) TFs and TGs co-evolve [dnaA and dnaN in E.coli, where D_dnaA = 3/(3 + 75) = 0.038 and D_dnaN = 9/(9 + 75) = 0.107]; (b) TF is evolutionarily more conserved than TG [fur and entD in E.coli, where D_fur = 70/(70 + 2) = 0.972 and D_entD = 0/(0 + 2) = 0] and (c) TF is less conserved than TG [metJ and ahpC in E.coli, where D_metJ = 1/(1 + 11) = 0.083 and D_ahpC = 81/(81 + 11) = 0.88].

Figure 4

Conservation of regulons across genomes clustered by the extent of TRN and regulon conservation for (a) E.coli K12 and (b) B.subtilis. The intensity of the color for each regulon in each genome indicates the percentage of total interactions in the regulon shared.

Figure 4

Conservation of regulons across genomes clustered by the extent of TRN and regulon conservation for (a) E.coli K12 and (b) B.subtilis. The intensity of the color for each regulon in each genome indicates the percentage of total interactions in the regulon shared.