Effector proteins translocated by the Dot/Icm type IV secretion system determine the virulence of (). Among these effectors, members of the SidE family (SidEs) regulate several cellular processes through a unique phosphoribosyl ubiquitination mechanism mediated by another effector, SidJ. Host-cell calmodulin (CaM) activates SidJ to glutamylate the SidEs of ubiquitin (Ub) ligases and to make a balanced Ub ligase activity. Given the central role of SidJ in this regulatory process, studying the nature of evolution of is important to understand the virulence of and the interaction between the bacteria and its hosts. By studying from a large number of strains and using various molecular evolution algorithms, we demonstrated that intragenic recombination drove the evolution of and contributed to diversification. Additionally, we showed that four codons of which are located in the N-terminal (NTD) (codons 58 and 200) and C-terminal (CTD) (codons 868 and 869) domains, but not in the kinase domain (KD) had been subjected to strong positive selection pressure, and variable mutation profiles of these codons were identified. Protein structural modeling of SidJ provided possible explanations for these mutations. Codons 868 and 869 mutations might engage in regulating the interactions of SidJ with CaM through hydrogen bonds and affect the CaM docking to SidJ. Mutation in codon 58 of SidJ might affect the distribution of main-chain atoms that are associated with the interaction with CaM. In contrast, mutations in codon 200 might influence the -helix stability in the NTD. These mutations might be important to balance Ub ligase activity for different hosts. This study first reported that intragenic recombination and positive Darwinian selection both shaped the genetic plasticity of , contributing to a deeper understanding of the adaptive mechanisms of this intracellular bacterium to different hosts.