Аннотация:The article presents the results of studies on the evolution of proteins from restriction–modification systems consisting of restriction endonucleases with the REase_AlwI family domain and either two DNA methyltransferases, each with the MethyltransfD12 family domain, or a single DNA methyltransferase with two domains of this family. It was found that all such systems recognized one of the three DNA sequences, namely GGATC, GATGC or GATGG. Based on the sequence similarity, restriction endonucleases of these systems could be attributed to three clades that unambiguously corresponded to the RM system specificity. TheDNA methyltransferase domains of these systems were classified into two groups based on sequence similarity, with the two domains of each system belonging to different groups. Within each group, the domains were attributed to three clades according to their specificity. An evidence of multiple interspecific horizontal transfer of entire restriction-modification systems has been found, as well as the transfer of individual genesbetween the systems (including the transfer of one of DNA methyltransferases accompanied by changes in its specificity). Evolutionary relationships of DNA methyltransferases from the studied systems with other DNA methyltransferases, including orphan DNA methyltransferases, have been revealed.