Nonplastid eukaryotic response regulators have a monophyletic origin and evolved from their bacterial precursors in parallel with their cognate sensor kinases.

We have analyzed all currently sequenced eukaryotic proteins containing either a kinase module or a receiver module, corresponding to those found in bacterial sensor kinases or response regulators, respectively, of the so-called two-component regulatory systems. We demonstrate that the eukaryotic receiver modules belong to a single subfamily of the bacterial receiver modules. Moreover, the cognate eukaryotic kinase modules exhibit a similar clustering pattern on the sensor kinase phylogenetic tree, suggesting that they evolved in parallel with the receiver modules from a common ancestral source that bore both modules. Multiple alignments of the sequences corresponding to these modules are presented and discussed, and eukaryotic-specific signature sequences are derived.