Editing Restriction modification system (section)

==Function==

''Neisseria meningitidis'' has multiple type II restriction endonuclease systems that are employed in natural [[Transformation (genetics)|genetic transformation]]. Natural genetic transformation is a process by which a recipient bacterial cell can take up DNA from a neighboring donor bacterial cell and integrate this DNA into its genome by recombination.  Although early work on restriction modification systems focused on the benefit to bacteria of protecting themselves against invading bacteriophage DNA or other foreign DNA, it is now known that these systems can also be used to restrict DNA introduced by natural transformation from other members of the same, or related species.{{cn|date=October 2022}}

In the pathogenic bacterium ''Neisseria meningitidis'' (meningococci), [[Natural competence|competence for transformation]] is a highly evolved and complex process where multiple proteins at the bacterial surface, in the membranes and in the cytoplasm interact with the incoming transforming DNA.  Restriction-modification systems are abundant in the genus ''Neisseria''.  ''N. meningitidis'' has multiple type II restriction endonuclease systems.<ref name=Budroni>{{cite journal |vauthors=Budroni S, Siena E, Dunning Hotopp JC, Seib KL, Serruto D, Nofroni C, Comanducci M, Riley DR, Daugherty SC, Angiuoli SV, Covacci A, Pizza M, Rappuoli R, Moxon ER, Tettelin H, Medini D |title=Neisseria meningitidis is structured in clades associated with restriction modification systems that modulate homologous recombination |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=108 |issue=11 |pages=4494–9 |year=2011 |pmid=21368196 |pmc=3060241 |doi=10.1073/pnas.1019751108 |bibcode=2011PNAS..108.4494B |doi-access=free }}</ref>  The restriction modification systems in ''N. meningitidis'' vary in specificity between different clades.<ref name=Budroni /><ref name="pmid10671450">{{cite journal |vauthors=Claus H, Friedrich A, Frosch M, Vogel U |title=Differential distribution of novel restriction-modification systems in clonal lineages of Neisseria meningitidis |journal=J. Bacteriol. |volume=182 |issue=5 |pages=1296–303 |year=2000 |pmid=10671450 |pmc=94415 |doi= 10.1128/jb.182.5.1296-1303.2000}}</ref>  This specificity provides an efficient barrier against DNA exchange between clades.<ref name=Budroni /> Luria, on page 99 of his autobiography,<ref name=Luria /> referred to such a restriction behavior as "an extreme instance of unfriendliness."  Restriction-modification appears to be a major driver of sexual isolation and speciation in the meningococci.<ref name="pmid22768309">{{cite journal |vauthors=Ambur OH, Frye SA, Nilsen M, Hovland E, Tønjum T |title=Restriction and sequence alterations affect DNA uptake sequence-dependent transformation in Neisseria meningitidis |journal=PLOS ONE |volume=7 |issue=7 |pages=e39742 |year=2012 |pmid=22768309 |pmc=3388099 |doi=10.1371/journal.pone.0039742 |bibcode=2012PLoSO...739742A |doi-access=free }}</ref>  Caugant and Maiden<ref name="pmid19464092">{{cite journal |vauthors=Caugant DA, Maiden MC |title=Meningococcal carriage and disease--population biology and evolution |journal=Vaccine |volume=27 Suppl 2 |pages=B64–70 |year=2009 |issue=4 |pmid=19464092 |pmc=2719693 |doi=10.1016/j.vaccine.2009.04.061 }}</ref> suggested that restriction-modification systems in meningococci may act to allow genetic exchange among very close relatives while reducing (but not completely preventing) genetic exchange among meningococci belonging to different clonal complexes and related species.{{cn|date=October 2022}}

RM systems can also act as [[selfish genetic elements]], forcing their maintenance on the cell through postsegregational cell killing.<ref>{{Cite journal|title=Restriction-Modification Systems as Genomic Parasites in Competition for Specific Sequences|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=92|issue=24|doi=10.1073/pnas.92.24.11095|pmid=7479944|pages=11095–11099|year=1995|vauthors=Kusano K|pmc=40578|bibcode=1995PNAS...9211095K|doi-access=free}}</ref>

Some viruses have evolved ways of subverting the restriction modification system, usually by modifying their own DNA, by adding methyl or [[glycosyl]] groups to it, thus blocking the restriction enzymes. Other viruses, such as bacteriophages T3 and T7, encode proteins that inhibit the restriction enzymes.{{cn|date=October 2022}}

To counteract these viruses, some bacteria have evolved restriction systems which only recognize and cleave modified DNA, but do not act upon the host's unmodified DNA. Some prokaryotes have developed multiple types of restriction modification systems.{{cn|date=October 2022}}

R-M systems are more abundant in promiscuous species, wherein they establish preferential paths of genetic exchange within and between lineages with cognate R-M systems.<ref>{{Cite journal|last1=Oliveira|first1=Pedro H.|last2=Touchon|first2=Marie|last3=Rocha|first3=Eduardo P.C.|date=2016-05-17|title=Regulation of genetic flux between bacteria by restriction–modification systems|journal=Proceedings of the National Academy of Sciences|language=en|volume=113|issue=20|pages=5658–5663|doi=10.1073/pnas.1603257113|issn=0027-8424|pmc=4878467|pmid=27140615|bibcode=2016PNAS..113.5658O|doi-access=free}}</ref> Because the repertoire and/or specificity of R-M systems in bacterial lineages vary quickly, the preferential fluxes of genetic transfer within species are expected to constantly change, producing time-dependent networks of gene transfer.{{cn|date=October 2022}}