Journal Article

Comprehensive Computational Analysis of Bacterial CRP/FNR Superfamily and Its Target Motifs Reveals Stepwise Evolution of Transcriptional Networks

Motomu Matsui, Masaru Tomita and Akio Kanai

in Genome Biology and Evolution

Published on behalf of Society for Molecular Biology and Evolution

Volume 5, issue 2, pages 267-282
Published in print January 2013 |
Published online January 2013 | e-ISSN: 1759-6653 | DOI:

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  • Bioinformatics and Computational Biology
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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 O2) 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.

Keywords: molecular evolution; phylogenetics; spectral clustering; transcription factor; cis-element

Journal Article.  7945 words.  Illustrated.

Subjects: Bioinformatics and Computational Biology ; Evolutionary Biology ; Genetics and Genomics

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