Quorum sensing is a widespread form of bacterial communication in which ind
ividual cells produce and respond to specific N-acyl homoserine lactone sig
nal metabolites. The different autoinducer synthases that generate these si
gnals and the receptor/activator proteins that mediate the cell's response
to them constitute evolutionarily conserved families of regulatory proteins
known as the LuxI and LuxR families, respectively. We have performed a phy
logenetic analysis of 76 individual LuxI and LuxR homologues present in div
erse members of the Gram-negative Proteobacteria. The results were consiste
nt with an early origin for these regulators during the evolution of the Pr
oteobacteria, with functional pairs of luxI and luxR genes possibly coevolv
ing as regulatory cassettes. In many cases, specific LuxI and LuxR family m
embers appeared to have been inherited horizontally. In particular, those s
pecies containing multiple LuxI and/or LuxR homologues usually appeared to
have obtained each individual homologue or functional pair of homologues fr
om an independent source. Because multiple homologues interact to form regu
latory cascades, this finding suggests that hierarchical signalling pathway
s can potentially evolve by the sequential integration of pre-existing regu
latory circuits acquired from diverse sources.