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Avoidance of recognition sites of restriction-modification (R-M) systems is a known anti-restriction strategy of prokaryotic viruses. We have recently demonstrated that only recognition sites of Type II R-M systems are commonly avoided in phage genomes [1], and also in prokaryotic genomes [2]. However, the avoidance of Type II restriction sites is not universal for either viruses or their hosts. We analysed Type II restriction site avoidance in genomes of phages and their hosts, separately considering 69 families of REase catalytic domains found in Type II R-M systems from REBASE. The data include complete genomes of 3870 prokaryotic viruses infecting 426 species of bacteria and archaea, and 4095 complete genomes of the prokaryotic species. R-M systems containing different domains unequally induce avoidance in genomes of both prokaryotes and their viruses. Recognition sites of DpnII and MutH-containing R-M systems are the most frequently avoided in phage genomes, BamHI and R-HINP1I-containing systems are the leaders in prokaryotes. R-M systems with ResIII and HNH_2 do not induce avoidance in phage or prokaryotic genomes. Site avoidance for different REase domains are mainly correlated between prokaryotes and their viruses (rho is 0.45). However some R-M systems have diverse effects on phages and bacteria. Thus, ThaI and RE_XamI domains induce avoidance in phages but not in bacteria, while RE_SacI and RE_Alw26IDE act oppositely. The work was supported by Russian Science Foundation grant 16-14-10319. 1. Rusinov et al., submitted to BMC Genomics. 2. Rusinov et al., BMC Genomics. 2015;16:1084.