How essential， regulatory genes originate and evolve is intriguing because mutations of these genes not only lead to lethality in organisms， but also have pleiotropic effects since they control the expression of multiple downstream genes. Therefore， the evolution of essential， regulatory genes is not only determined by genetic variations of their own sequences， but also by the biological function of downstream genes and molecular mechanisms of regulation. To understand the origin of essential， regulatory genes， experimental dissection of the complete regulatory cascade is needed. Here， we provide genetic evidences to reveal that PhoP-PhoQ is an essential two-component signal transduction system in the gram-negative bacterium ， but that its orthologs in other bacteria belonging to Proteobacteria are nonessential. Mutational， biochemical， and chromatin immunoprecipitation together with high-throughput sequencing analyses revealed that and of and its close relative are replaceable， and that the consensus binding motifs of the transcription factor PhoP are also highly conserved. PhoP in regulates the transcription of a number of essential， structural genes by directly binding to -regulatory elements (CREs); however， these CREs are lacking in the orthologous essential， structural genes in ， and thus the regulatory relationships between PhoP and these downstream essential genes are disassociated. Our findings suggested that the recruitment of regulatory proteins by critical structural genes via transcription factor-CRE rewiring is a driving force in the origin and functional divergence of essential， regulatory genes.