Background: The two-component signaling (TCS) system is an important signal transduction
machinery in prokaryotes and eukaryotes, excluding animals, that uses a protein phosphorylation
mechanism for signal transmission.
Conclusion: Prokaryotes have a primitive type of TCS machinery, which mainly comprises a membrane-
bound sensory histidine kinase (HK) and its cognate cytoplasmic response regulator (RR).
Hence, it is sometimes referred to as two-step phosphorelay (TSP). Eukaryotes have more sophisticated
signaling machinery, with an extra component - a histidine-containing phosphotransfer (HPT)
protein that shuttles between HK and RR to communicate signal baggage. As a result, the TSP
has evolved from a two-step phosphorelay (His–Asp) in simple prokaryotes to a multi-step phosphorelay
(MSP) cascade (His–Asp–His–Asp) in complex eukaryotic organisms, such as plants, to
mediate the signaling network. This molecular evolution is also reflected in the form of considerable
structural modifications in the domain architecture of the individual components of the TCS
system. In this review, we present TCS system's evolutionary journey from the primitive TSP to advanced
MSP type across the genera. This information will be highly useful in designing the future
strategies of crop improvement based on the individual members of the TCS machinery.