## 6 Conclusions and Open Problems  
We can conclude that the topological patterns in QS genes seem to follow a few basic rules--such as the conservation of genes between luxR and luxI genes, repeating patterns in certain taxa, _etc._--but their variety is apparently greater than previously indicated [35,36]. The clustering of QS genes suggests that the topological units might act as regulatory modules that evolve together. In order to further test these hypotheses, we plan to widen the scope of the analyzed databases so as to include in the survey draft genomes and individually sequenced genomic regions. We also plan to pinpoint conserved DNA motifs within the neighborhood of the QS circuits. Maintaining and manually curating such a collection is beyond the possibilities of a single research group. Rather, we consider using bioinformatic tools for updating the current collection in the form of an openly accessible Internet repository so that researchers of the field could add their own annotations in the future.  
This work is a preliminary, computational census of topological patterns found in complete proteobacterial genomes. It is expected that other kind of patterns may be found in published papers and in other sources, especially draft genomes, and we plan to develop computational protocols for finding these occurrences. On the other hand, there are a number of problems that are not touched upon in our work but may be answered as more detailed data become available. First, are the topological patterns associated with distinct biological functions? As QS circuits are involved in activating a large variety of genes in various bacteria, we speculate that there may be no simple correspondence between  
Figure 2: Clustering of LuxI and their negative regulators RasL shows identical tendencies. (**A**) shows tree of LuxI proteins present RI and RLI pattern, and (**B**) shows RasL proteins in RLI pattern. The sequences were taken from genomes harboring _rsaL_ genes located between _luxR_ and _luxI_ genes. The clustering was carried out by the Phylip program package [52]. The numerical value at each node indicates the bootstrap value supporting every split in the lineage (out of 1,000 bootstrap replicates).  
topology and the regulated functions. While we agree that these questions should be tackled by experiment, some supporting evidence can be gathered by comparing the gene neighborhood of QS circuits. The intervening genes (which are a conspicuous subgroup of neighborhood genes) appear to belong to only a few types, and in some genomes they are also found outside the immediate vicinity of QS genes. Another avenue would be to categorize the QS patterns according to the chemical nature of the signals produced by the _luxI_ and/or sensed by the _luxR_ gene.  
The present classification suggests that the patterns seem to be relatively conserved and their distribution among the various taxonomic groups is not random. This does not mean that one can make broad statements about the functional reasons of this apparent conservation. We tend to speculate that the known principles of gene expression (co-transcription, repression by proteins or RNA) can be combined into a finite set of topological patterns that allow stable positive autoregulation and control of linked genes. It would be tempting to speculate that such modules then can move between genomes but this problem, as well as further evolutionary questions are outside the immediate scope of the present paper.