Bellieny-Rabelo, DanielPretorius, Willem J.S.Moleleki, Lucy Novungayo2022-03-092022-03-092021-03Bellieny-Rabelo, D., Pretorius, W.J.S. & Moleleki, L.N. 2021, 'Novel two-component system-like elements reveal functional domains associated with restriction-modification systems and paraMORC ATPases in bacteria', Genome Biology and Evolution, vol. 13, no. 3, pp. 1-15.1759-665310.1093/gbe/evab024http://hdl.handle.net/2263/84391Two-component systems (TCS) are important types of machinery allowing for efficient signal recognition and transmission in bacterial cells. The majority of TCSs utilized by bacteria is composed of a sensor histidine kinase (HK) and a cognate response regulator (RR). In the present study,we report two newly predicted protein domains—both to be included in the next release of the Pfamdatabase: Response_reg_2 (PF19192) andHEF_HK(PF19191)—in bacteriawhich exhibit high structural similarity, respectively, with typical domains of RRs and HKs. Additionally, the genes encoding for the novel predicted domains exhibit a 91.6% linkage observed across 644 genomic regions recovered from 628 different bacterial strains. The remarkable adjacent colocalization between genes carrying Response_reg_2 and HEF_HK in addition to their conserved structural features, which are highly similar to those fromwell-known HKs and RRs, raises the possibility of Response_reg_2 and HEF_HK constituting a new TCS in bacteria. The genomic regions inwhich these predicted two-component systems-like are located additionally exhibit an overrepresented presence of restriction–modification (R–M) systems especially the type II R–M. Among these, there is a conspicuous presence of C-5 cytosinespecific DNAmethylaseswhichmay indicate a functional associationwith the newly discovered domains. The solid presence of R–M systems and the presence of theGHKL family domain HATPase_c_3 across most of the HEF_HK-containing genes are also indicative that these genes are evolutionarily related to the paraMORC family of ATPases.en© The Author(s) 2021. This is an Open Access article distributed under the terms of the Creative Commons Attribution License.MORCGHKL ATPasesDNA modification methylasesDNA restriction–modification enzymesHistidine kinaseTwo-component system (TCS)Deoxyribonucleic acid (DNA)Article