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Reconstruction of the core and extended regulons of global transcription factors.

Dufour YS, Kiley PJ, Donohue TJ - PLoS Genet. (2010)

Bottom Line: Our results show that this approach correctly predicted many regulon members, provided new insights into the biological functions of the respective regulons for these regulators, and suggested models for the evolution of the corresponding transcriptional networks.In addition, the members of the so-called extended regulons for the FNR-type regulators vary even among closely related species, possibly reflecting species-specific adaptation to environmental and other factors.The comparative genomics approach we developed is readily applicable to other regulatory networks.

View Article: PubMed Central - PubMed

Affiliation: Department of Bacteriology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.

ABSTRACT
The processes underlying the evolution of regulatory networks are unclear. To address this question, we used a comparative genomics approach that takes advantage of the large number of sequenced bacterial genomes to predict conserved and variable members of transcriptional regulatory networks across phylogenetically related organisms. Specifically, we developed a computational method to predict the conserved regulons of transcription factors across alpha-proteobacteria. We focused on the CRP/FNR super-family of transcription factors because it contains several well-characterized members, such as FNR, FixK, and DNR. While FNR, FixK, and DNR are each proposed to regulate different aspects of anaerobic metabolism, they are predicted to recognize very similar DNA target sequences, and they occur in various combinations among individual alpha-proteobacterial species. In this study, the composition of the respective FNR, FixK, or DNR conserved regulons across 87 alpha-proteobacterial species was predicted by comparing the phylogenetic profiles of the regulators with the profiles of putative target genes. The utility of our predictions was evaluated by experimentally characterizing the FnrL regulon (a FNR-type regulator) in the alpha-proteobacterium Rhodobacter sphaeroides. Our results show that this approach correctly predicted many regulon members, provided new insights into the biological functions of the respective regulons for these regulators, and suggested models for the evolution of the corresponding transcriptional networks. Our findings also predict that, at least for the FNR-type regulators, there is a core set of target genes conserved across many species. In addition, the members of the so-called extended regulons for the FNR-type regulators vary even among closely related species, possibly reflecting species-specific adaptation to environmental and other factors. The comparative genomics approach we developed is readily applicable to other regulatory networks.

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The predicted conservation of the FnrL regulon determined in R. sphaeroides across α-proteobacteria.Orange and yellow indicate respectively moderate and strong match to the DNA target sequence position-weighted matrix. Black indicates that the corresponding species possesses a gene belonging to the corresponding set of orthologs, while grey indicates that the species does not possess an orthologous gene. Sets of orthologous genes are labeled with arbitrary numbers. The core FNR regulon, as determined in Figure 4, and the extended FnrL regulon, determined in R. sphaeroides, are indicated by arrows below the sets of ortholog labels. Species are organized according to the phylogenetic tree presented in Figure S1.
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pgen-1001027-g007: The predicted conservation of the FnrL regulon determined in R. sphaeroides across α-proteobacteria.Orange and yellow indicate respectively moderate and strong match to the DNA target sequence position-weighted matrix. Black indicates that the corresponding species possesses a gene belonging to the corresponding set of orthologs, while grey indicates that the species does not possess an orthologous gene. Sets of orthologous genes are labeled with arbitrary numbers. The core FNR regulon, as determined in Figure 4, and the extended FnrL regulon, determined in R. sphaeroides, are indicated by arrows below the sets of ortholog labels. Species are organized according to the phylogenetic tree presented in Figure S1.

Mentions: Nevertheless, the size of the experimentally determined R. sphaeroides FnrL regulon (68 genes) is larger than the one proposed to be conserved across α-proteobacteria (20 sets of orthologs); leaving us without information about the regulation of ∼50 predicted FnrL target genes in other α-proteobacteria. Our comparative genomics analysis selected only target genes that were conserved in at least in 20% of the species possessing FNR orthologs. Therefore, to examine to what extent the additional ∼50 genes of the R. sphaeroides FnrL regulon were conserved within the 87 α-proteobacteria, we identified the sets of orthologous genes among these bacteria that corresponded to the FnrL target genes and determined which of their promoters contained a predicted FNR DNA target sequence. The results of this analysis indicated that very few of the other α-proteobacteria have FNR target genes in common with R. sphaeroides beyond the 20 conserved sets of orthologs (Figure 7, Table S2). As expected, the predicted FNR regulon of another R. sphaeroides strain (ATCC 17025) overlaps significantly with the FnrL regulon of R. sphaeroides 2.4.1. In addition, only the FNR regulons of the R. palustris strains TIE-1 and HaA2, which are photosynthetic bacteria, were predicted to have a significant number of orthologous genes with the extended R. sphaeroides FnrL regulon. Interestingly, the predicted overlap of the FnrL regulons between R. sphaeroides strain 2.4.1 and R. palustris strains TIE-1 and HaA2 is larger than the overlap between R. sphaeroides and more closely related species of the Rhodobacterales order.


Reconstruction of the core and extended regulons of global transcription factors.

Dufour YS, Kiley PJ, Donohue TJ - PLoS Genet. (2010)

The predicted conservation of the FnrL regulon determined in R. sphaeroides across α-proteobacteria.Orange and yellow indicate respectively moderate and strong match to the DNA target sequence position-weighted matrix. Black indicates that the corresponding species possesses a gene belonging to the corresponding set of orthologs, while grey indicates that the species does not possess an orthologous gene. Sets of orthologous genes are labeled with arbitrary numbers. The core FNR regulon, as determined in Figure 4, and the extended FnrL regulon, determined in R. sphaeroides, are indicated by arrows below the sets of ortholog labels. Species are organized according to the phylogenetic tree presented in Figure S1.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2908626&req=5

pgen-1001027-g007: The predicted conservation of the FnrL regulon determined in R. sphaeroides across α-proteobacteria.Orange and yellow indicate respectively moderate and strong match to the DNA target sequence position-weighted matrix. Black indicates that the corresponding species possesses a gene belonging to the corresponding set of orthologs, while grey indicates that the species does not possess an orthologous gene. Sets of orthologous genes are labeled with arbitrary numbers. The core FNR regulon, as determined in Figure 4, and the extended FnrL regulon, determined in R. sphaeroides, are indicated by arrows below the sets of ortholog labels. Species are organized according to the phylogenetic tree presented in Figure S1.
Mentions: Nevertheless, the size of the experimentally determined R. sphaeroides FnrL regulon (68 genes) is larger than the one proposed to be conserved across α-proteobacteria (20 sets of orthologs); leaving us without information about the regulation of ∼50 predicted FnrL target genes in other α-proteobacteria. Our comparative genomics analysis selected only target genes that were conserved in at least in 20% of the species possessing FNR orthologs. Therefore, to examine to what extent the additional ∼50 genes of the R. sphaeroides FnrL regulon were conserved within the 87 α-proteobacteria, we identified the sets of orthologous genes among these bacteria that corresponded to the FnrL target genes and determined which of their promoters contained a predicted FNR DNA target sequence. The results of this analysis indicated that very few of the other α-proteobacteria have FNR target genes in common with R. sphaeroides beyond the 20 conserved sets of orthologs (Figure 7, Table S2). As expected, the predicted FNR regulon of another R. sphaeroides strain (ATCC 17025) overlaps significantly with the FnrL regulon of R. sphaeroides 2.4.1. In addition, only the FNR regulons of the R. palustris strains TIE-1 and HaA2, which are photosynthetic bacteria, were predicted to have a significant number of orthologous genes with the extended R. sphaeroides FnrL regulon. Interestingly, the predicted overlap of the FnrL regulons between R. sphaeroides strain 2.4.1 and R. palustris strains TIE-1 and HaA2 is larger than the overlap between R. sphaeroides and more closely related species of the Rhodobacterales order.

Bottom Line: Our results show that this approach correctly predicted many regulon members, provided new insights into the biological functions of the respective regulons for these regulators, and suggested models for the evolution of the corresponding transcriptional networks.In addition, the members of the so-called extended regulons for the FNR-type regulators vary even among closely related species, possibly reflecting species-specific adaptation to environmental and other factors.The comparative genomics approach we developed is readily applicable to other regulatory networks.

View Article: PubMed Central - PubMed

Affiliation: Department of Bacteriology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.

ABSTRACT
The processes underlying the evolution of regulatory networks are unclear. To address this question, we used a comparative genomics approach that takes advantage of the large number of sequenced bacterial genomes to predict conserved and variable members of transcriptional regulatory networks across phylogenetically related organisms. Specifically, we developed a computational method to predict the conserved regulons of transcription factors across alpha-proteobacteria. We focused on the CRP/FNR super-family of transcription factors because it contains several well-characterized members, such as FNR, FixK, and DNR. While FNR, FixK, and DNR are each proposed to regulate different aspects of anaerobic metabolism, they are predicted to recognize very similar DNA target sequences, and they occur in various combinations among individual alpha-proteobacterial species. In this study, the composition of the respective FNR, FixK, or DNR conserved regulons across 87 alpha-proteobacterial species was predicted by comparing the phylogenetic profiles of the regulators with the profiles of putative target genes. The utility of our predictions was evaluated by experimentally characterizing the FnrL regulon (a FNR-type regulator) in the alpha-proteobacterium Rhodobacter sphaeroides. Our results show that this approach correctly predicted many regulon members, provided new insights into the biological functions of the respective regulons for these regulators, and suggested models for the evolution of the corresponding transcriptional networks. Our findings also predict that, at least for the FNR-type regulators, there is a core set of target genes conserved across many species. In addition, the members of the so-called extended regulons for the FNR-type regulators vary even among closely related species, possibly reflecting species-specific adaptation to environmental and other factors. The comparative genomics approach we developed is readily applicable to other regulatory networks.

Show MeSH