Conservation of the binding site for the arginine repressor in all bacterial lineages

Abstract

and some other genomes. Here, we apply the comparative genomic approach to the prediction of the ArgR-binding sites in all completely sequenced bacterial genomes. Candidate arginine repressor binding sites were identified upstream of arginine transport and metabolism genes. ) belonging to the candidate arginine regulons.

Background:

and some other genomes. Here, we apply the comparative genomic approach to the prediction of the ArgR-binding sites in all completely sequenced bacterial genomes.

Results:

Candidate arginine repressor binding sites were identified upstream of arginine transport and metabolism genes.

Conclusions:

) belonging to the candidate arginine regulons.

Background

). A comparison of the coevolution of these conserved regulators and their binding sites in DNA could reveal general trends in the evolution of regulons.

).

].

regulon as the starting point. Here we extend this analysis to explore the conservation of the ARG box in all bacteria that encode an ortholog of the ArgR repressor.

Results and discussion

The comparative approach to the analysis of regulation is based on the assumption that regulons (sets of co-regulated genes) are conserved in genomes containing orthologs of the relevant regulatory proteins. Thus true candidate binding sites for the regulator occur upstream of orthologous genes, whereas false positives are scattered at random in the genome. This provides a consistency check that sharply increases the accuracy of prediction.

] (data not shown).

gene encoding an arginine utilization protein with unknown biochemical function. Thus is it likely that YqjN has the same function as RocB and is also involved in arginine degradation.

have no candidate ARG boxes and do not seem to belong to the arginine regulon.

].

profile, but not with the gamma-proteobacteria profile.

).

Conclusions

].

In contrast, CIRCE elements appear to be direct descendants of the ancient regulon present in the common ancestor of the Bacteria, because the variation in the composition of the CIRCE regulon is minimal and the few additional sites found in some genomes are apparently products of duplication. Most other DNA-binding domains of transcriptional regulators (including LexA) seem to undergo considerable changes together with their DNA signals and regulons. Thus, the evolution of the arginine regulon and ARG boxes seems to reflect a tradeoff between maintaining regulon flexibility on one hand and retaining the universal regulatory mechanism on the other.

].

], will enable us to make this comparison. On the other hand, we feel that the predictions made in this study, especially identification of the Art family ABC transporters in several diverse genomes, are sufficiently interesting to warrant experimental verification.

Materials and methods

]. Only genes having candidate sites in five or more out of the eight genomes analyzed were considered as candidate regulon members and were retained for further analysis. This procedure could lead to the loss of some true sites, but ensured that false sites were not accepted.

].

Acknowledgements

We thank Eugene Koonin, Yury Kozlov and Igor Rogosin for useful discussions. This study was partially supported by grants from the Merck Genome Research Institute (244), the Russian Fund of Basic Research (99-04-48247 and 00-15-99362), the Russian State Scientific Program 'Human Genome', INTAS (99-1476), the Howard Hughes Medical Institute (55000309), and Microbial Genome Program, Office of Biological and Environmental Research, DOE (DE-FG02-98ER62583).

Figures and Tables

[14] (data not shown). The transporter genes are: periplasmic binding protein (white), permease transmembrane protein (light gray), ATPase component (dark gray).

. Experimentally established specificity of transporters is indicated in parentheses. Genes with candidate ARG boxes in upstream regions are shown in italic and in a larger font.

Comparison of three transcriptional regulator families with predominantly single representatives from each bacterial genome

The 'winged helix' superfamily is defined in the SCOP database [40]; LexA [41] and ArgR [42,43,44] DNA-binding domains have been resolved by X-ray crystallography. The same type of domain was predicted for HrsA using PSIBLAST program.

Candidate ARG boxes upstream of arginine metabolism related genes and operons

candidate ARG boxes using the procedure from [28]. The sites used to construct the profile are shown in bold.