title: Comprehensive computational analysis of bacterial CRP/FNR superfamily and its target motifs reveals stepwise evolution of transcriptional networks.
abstract: The cAMP receptor protein (CRP)/fumarate and nitrate reduction regulatory protein (FNR)-type transcription factors (TFs) are members of a well-characterized global TF family in bacteria and have two conserved domains: the N-terminal ligand-binding domain for small molecules (e.g., cAMP, NO, or O(2)) and the C-terminal DNA-binding domain. Although the CRP/FNR-type TFs recognize very similar consensus DNA target sequences, they can regulate different sets of genes in response to environmental signals. To clarify the evolution of the CRP/FNR-type TFs throughout the bacterial kingdom, we undertook a comprehensive computational analysis of a large number of annotated CRP/FNR-type TFs and the corresponding bacterial genomes. Based on the amino acid sequence similarities among 1,455 annotated CRP/FNR-type TFs, spectral clustering classified the TFs into 12 representative groups, and stepwise clustering allowed us to propose a possible process of protein evolution. Although each cluster mainly consists of functionally distinct members (e.g., CRP, NTC, FNR-like protein, and FixK), FNR-related TFs are found in several groups and are distributed in a wide range of bacterial phyla in the sequence similarity network. This result suggests that the CRP/FNR-type TFs originated from an ancestral FNR protein, involved in nitrogen fixation. Furthermore, a phylogenetic profiling analysis showed that combinations of TFs and their target genes have fluctuated dynamically during bacterial evolution. A genome-wide analysis of TF-binding sites also suggested that the diversity of the transcriptional regulatory system was derived by the stepwise adaptation of TF-binding sites to the evolution of TFs.
authors: Institute for Advanced Biosciences, Keio University, Tsuruoka, Japan.
authors: Motomu
authors: M
authors: Matsui
authors: Masaru
authors: M
authors: Tomita
authors: Akio
authors: A
authors: Kanai
mesh_terms: D001419:Bacteria / Q000235:genetics*; D019295:Computational Biology; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins / Q000235:genetics*; D019143:Evolution, Molecular; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks / Q000235:genetics; D016680:Genome, Bacterial; D007506:Iron-Sulfur Proteins / Q000235:genetics*; D005810:Multigene Family; D059372:Nucleotide Motifs; D010802:Phylogeny
chemical_list: D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C060704:FNR protein, E coli; D007506:Iron-Sulfur Proteins