Institute for Advanced Biosciences, Keio University, Tsuruoka, Japan.
Genome Biol Evol. 2013;5(2):267-82. doi: 10.1093/gbe/evt004.
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.
cAMP 受体蛋白 (CRP)/延胡索酸和硝酸盐还原调节蛋白 (FNR)-型转录因子 (TF) 是细菌中一类特征明确的全局 TF 家族的成员，具有两个保守结构域：小分子（如 cAMP、NO 或 O(2)）结合的 N 端配体结合域和 C 端 DNA 结合域。尽管 CRP/FNR 型 TFs 识别非常相似的一致 DNA 靶序列，但它们可以响应环境信号调节不同的基因集。为了阐明 CRP/FNR 型 TFs 在整个细菌王国中的进化历程，我们对大量注释的 CRP/FNR 型 TFs 和相应的细菌基因组进行了全面的计算分析。基于 1455 个注释的 CRP/FNR 型 TFs 的氨基酸序列相似性，谱聚类将 TFs 分为 12 个有代表性的组，逐步聚类使我们能够提出一种可能的蛋白质进化过程。虽然每个聚类主要由功能不同的成员（如 CRP、NTC、FNR 样蛋白和 FixK）组成，但在序列相似性网络中，FNR 相关的 TFs 存在于几个组中，并分布在细菌门的广泛范围内。这一结果表明，CRP/FNR 型 TFs 起源于参与固氮作用的祖先 FNR 蛋白。此外，系统发育分析表明，TF 及其靶基因的组合在细菌进化过程中动态波动。TF 结合位点的全基因组分析也表明，转录调控系统的多样性是通过 TF 结合位点逐步适应 TF 的进化而产生的。
