<p>The two-component system (TCS), a molecular team comprising three groups of genes: histidine kinase (HK), histidine-containing phosphotransmitter (HPT), and response regulators (RR), is a crucial and one of the most conserved signaling cascades in plants. It plays a key role in ethylene and cytokinin signalling and affects many developmental as well as stress-responsive processes and pathways. The TCS genes were found to be expressed in both climacteric and non-climacteric fruits; however, the regulation of ripening by ethylene only occurs in climacteric fruits. This study examines the evolution of TCS genes in both climacteric and non-climacteric fruits to identify the key differences in their response to ethylene-mediated fruit ripening. The evolutionary analysis of the CHK (CHASE-containing HK) and ERS (Ethylene Response Sensor) genes reveals their early divergence, as indicated by their monocot-dicot specificity. Thus, the evolutionary changes in the HK domains in plants were related to the hormonal specificity, CHK for cytokinin, and ERS for ethylene. The evolutionary changes in the CHASE (Cyclase/Histidine kinase Associated Sensory Extracellular) and GAF (cGMP-specific phosphodiesterases, adenylyl cyclases, and FhlA) domains do not exhibit any discernible pattern related to their climacteric or non-climacteric nature. However, the transcriptomic analysis of the TCS module during fruit ripening shows higher expression of TCS genes during ripening in climacteric fruits. The epigenetic analysis also revealed differential regulation of the ERS genes in climacteric fruits, indicating that epigenetic regulation controls the differential behavior of the TCS genes in climacteric and non-climacteric fruits. The present study explores and elucidates the genomic and epigenetic influence of the TCS gene family in plants during various stages of the fruit ripening process. </p>