Restriction–Modification Systems Specific toward GGATC, GATGC, and GATGG. Part 1. Evolution and Ecology

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Sergey Spirin^1,2,3,a*, Ivan Rusinov¹, Olga Makarikova⁴, Andrei Alexeevski^1,3, Anna Karyagina^1,5,6

¹Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119234 Moscow, Russia

²Higher School of Economics National Research University, 109028 Moscow, Russia

³NRC “Kurchatov Institute” - SRISA, 117218 Moscow, Russia

⁴Moscow Institute of Physics and Technology, 117303 Moscow, Russia

⁵Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Healthcare of the Russian Federation, 123098 Moscow, Russia

⁶All-Russia Research Institute of Agricultural Biotechnology, 127550 Moscow, Russia

^* To whom correspondence should be addressed.

Received: January 21, 2025; Revised: March 19, 2025; Accepted: March 25, 2025

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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. The DNA 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 genes between 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.

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KEY WORDS: restriction–modification system, molecular evolution, DNA methyltransferase, restriction endonuclease, horizontal gene transfer

DOI: 10.1134/S0006297925600115

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