title: Lifespan of restriction-modification systems critically affects avoidance of their recognition sites in host genomes.
abstract: BACKGROUND
  Avoidance of palindromic recognition sites of Type II restriction-modification (R-M) systems was shown for many R-M systems in dozens of prokaryotic genomes. However the phenomenon has not been investigated systematically for all presently available genomes and annotated R-M systems. We have studied all known recognition sites in thousands of prokaryotic genomes and found factors that influence their avoidance.
  
  
  RESULTS
  Only Type II R-M systems consisting of independently acting endonuclease and methyltransferase (called 'orthodox' here) cause avoidance of their sites, both palindromic and asymmetric, in corresponding prokaryotic genomes; the avoidance takes place for ~ 50 % of 1774 studied cases. It is known that prokaryotes can acquire and lose R-M systems. Thus it is possible to talk about the lifespan of an R-M system in a genome. We have shown that the recognition site avoidance correlates with the lifespan of R-M systems. The sites of orthodox R-M systems that are encoded in host genomes for a long time are avoided more often (up to 100 % in certain cohorts) than the sites of recently acquired ones. We also found cases of site avoidance in absence of the corresponding R-M systems in the genome. An analysis of closely related bacteria shows that such avoidance can be a trace of lost R-M systems. Sites of Type I, IIС/G, IIM, III, and IV R-M systems are not avoided in vast majority of cases.
  
  
  CONCLUSIONS
  The avoidance of orthodox Type II R-M system recognition sites in prokaryotic genomes is a widespread phenomenon. Presence of an R-M system without an underrepresentation of its site may indicate that the R-M system was acquired recently. At the same time, a significant underrepresentation of a site may be a sign of presence of the corresponding R-M system in this organism or in its ancestors for a long time. The drastic difference between site avoidance for orthodox Type II R-M systems and R-M systems of other types can be explained by a higher rate of specificity changes or a less self-toxicity of the latter.
authors.affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, 119992, Russia. isrusinov@gmail.com.
authors.forename: Ivan
authors.initials: I
authors.lastname: Rusinov
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992, Russia. asershova@gmail.com.|Gamaleya Center of Epidemiology and Microbiology, Moscow, 123098, Russia. asershova@gmail.com.|Institute of Agricultural Biotechnology, the Russian Academy of Sciences, Moscow, 127550, Russia. asershova@gmail.com.
authors.forename: Anna
authors.initials: A
authors.lastname: Ershova
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992, Russia. akaryagina@gmail.com.|Gamaleya Center of Epidemiology and Microbiology, Moscow, 123098, Russia. akaryagina@gmail.com.|Institute of Agricultural Biotechnology, the Russian Academy of Sciences, Moscow, 127550, Russia. akaryagina@gmail.com.
authors.forename: Anna
authors.initials: A
authors.lastname: Karyagina
authors.affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, 119992, Russia. sas@belozersky.msu.ru.|Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992, Russia. sas@belozersky.msu.ru.|Scientific Research Institute for System Studies, the Russian Academy of Science (NIISI RAS), Moscow, 117281, Russia. sas@belozersky.msu.ru.
authors.forename: Sergey
authors.initials: S
authors.lastname: Spirin
authors.affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, 119992, Russia. aba@belozersky.msu.ru.|Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992, Russia. aba@belozersky.msu.ru.|Scientific Research Institute for System Studies, the Russian Academy of Science (NIISI RAS), Moscow, 117281, Russia. aba@belozersky.msu.ru.
authors.forename: Andrei
authors.initials: A
authors.lastname: Alexeevski
mesh_terms: D019175:DNA Methylation; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism*; D064349:Genome, Microbial; D055029:Inverted Repeat Sequences; D015183:Restriction Mapping
chemical_list: D015252:Deoxyribonucleases, Type II Site-Specific