Regulatory relationship of two-component and ABC transport systems and clustering of their genes in the Bacillus/Clostridium group, suggest a functional link between them.

On the Bacillus subtilis chromosome there are five examples of genes encoding two-component systems with response regulators of the OmpR family adjacent to genes encoding sub-family 9 ABC transport systems. Three of these (yts, yvc, yxd) are very similar in gene organization and in sequence. We demonstrate that the TCS and ABC transporter genes do not belong to the same transcriptional unit. The ABC transport and TCS systems are functionally linked, each response regulator controlling the expression of its cognate ABC transporter genes but not its own. Analysis of 48 bacterial genomes revealed that such family clusters only exist in the Bacillus/Clostridium group. Evolutionary analyses indicated that almost all clustered OmpR response regulators constitute two groups ("GI" and "GIIl") whereas almost all clustered sub-family 9 nucleotide-binding domains belong to two other groups ("9A" and "9B"). Interestingly, there is a mutually exclusive clustering between genes encoding "GI" or a "GII" response regulators and genes encoding "9A" or a "9B" nucleotide binding proteins. We propose that a two-component system and its cognate ABC transporter genes have evolved as a unit in Bacillus/Clostridium, both systems participating in a common physiological process.