Sensor and output domains are versatile in structure and function, whereas transmitters and receivers are highly conserved. (A) In TCS systems such as EnvZ/OmpR (blue linkers), the HK comprises a sensor domain and transmitter domain and the RR protein is composed of receiver and output domain. In other TCS systems, the receiver and output functions act in trans. (B) In more complex phosphorelays, additional receiver transmitter modules are found and may serve to integrate additional inputs into the signalling pathway. The phosphotransfer is directional from transmitter histidine to receiver aspartate to transmitter histidine and so forth. We speculate that the differences in cis/trans domain linkage in TCS may realize particular signalling requirements and trade-offs with regards to signalling fidelity, network complexity and control stringency (see the text for details).