Diversity-generating retroelement
Diversity-generating retroelements (DGRs) are a family of retroelements that were first found in Bordetella phage (BPP-1),{{Cite journal|last1=Doulatov|first1=Sergei|last2=Hodes|first2=Asher|last3=Dai|first3=Lixin|last4=Mandhana|first4=Neeraj|last5=Liu|first5=Minghsun|last6=Deora|first6=Rajendar|last7=Simons|first7=Robert W.|last8=Zimmerly|first8=Steven|last9=Miller|first9=Jeff F.|date=2004-09-30|title=Tropism switching in Bordetella bacteriophage defines a family of diversity-generating retroelements|url=http://dx.doi.org/10.1038/nature02833|journal=Nature|volume=431|issue=7007|pages=476–481|doi=10.1038/nature02833|pmid=15386016|bibcode=2004Natur.431..476D|s2cid=1849829|issn=0028-0836|url-access=subscription}} and since been found in bacteria (e.g.Treponema denticola{{Cite journal|last1=Nimkulrat|first1=Sutichot|last2=Lee|first2=Heewook|last3=Doak|first3=Thomas G.|last4=Ye|first4=Yuzhen|date=2016-06-03|title=Genomic and Metagenomic Analysis of Diversity-Generating Retroelements Associated with Treponema denticola|journal=Frontiers in Microbiology|volume=7|page=852|doi=10.3389/fmicb.2016.00852|pmid=27375574|pmc=4891356|issn=1664-302X|doi-access=free}} and Legionella pneumophila{{Cite journal|last1=Arambula|first1=D.|last2=Wong|first2=W.|last3=Medhekar|first3=B. A.|last4=Guo|first4=H.|last5=Gingery|first5=M.|last6=Czornyj|first6=E.|last7=Liu|first7=M.|last8=Dey|first8=S.|last9=Ghosh|first9=P.|last10=Miller|first10=J. F.|date=2013-04-30|title=Surface display of a massively variable lipoprotein by a Legionella diversity-generating retroelement|journal=Proceedings of the National Academy of Sciences|volume=110|issue=20|pages=8212–8217|doi=10.1073/pnas.1301366110 |pmid=23633572| pmc=3657778 |bibcode=2013PNAS..110.8212A|issn=0027-8424|doi-access=free}}), Archaea, Archaean viruses (e.g. ANMV-1),{{Cite journal|last1=Paul|first1=Blair G.|last2=Bagby|first2=Sarah C.|last3=Czornyj|first3=Elizabeth|last4=Arambula|first4=Diego|last5=Handa|first5=Sumit|last6=Sczyrba|first6=Alexander|last7=Ghosh|first7=Partho|last8=Miller|first8=Jeff F.|last9=Valentine|first9=David L.|date=2015-03-23|title=Targeted diversity generation by intraterrestrial archaea and archaeal viruses|journal=Nature Communications|volume=6|issue=1|page=6585|doi=10.1038/ncomms7585|pmid=25798780|pmc=4372165|bibcode=2015NatCo...6.6585P|issn=2041-1723|doi-access=free}} temperate phages (e.g. Hankyphage{{Cite journal|last1=Benler|first1=Sean|last2=Cobián-Güemes|first2=Ana Georgina|last3=McNair|first3=Katelyn|last4=Hung|first4=Shr-Hau|last5=Levi|first5=Kyle|last6=Edwards|first6=Rob|last7=Rohwer|first7=Forest|date=2018-10-23|title=A diversity-generating retroelement encoded by a globally ubiquitous Bacteroides phage|journal=Microbiome|volume=6|issue=1|page=191|doi=10.1186/s40168-018-0573-6|pmid=30352623|pmc=6199706|issn=2049-2618|doi-access=free}} and CrAss-like phage{{Cite journal|last1=Morozova|first1=Vera|last2=Fofanov|first2=Mikhail|last3=Tikunova|first3=Nina|last4=Babkin|first4=Igor|last5=Morozov|first5=Vitaliy V.|last6=Tikunov|first6=Artem|date=2020-05-22|title=First crAss-Like Phage Genome Encoding the Diversity-Generating Retroelement (DGR)|journal=Viruses|volume=12|issue=5|pages=573|doi=10.3390/v12050573 |pmid=32456083|pmc=7290462|issn=1999-4915|doi-access=free}}), and lytic phages.{{Cite journal|last1=Hedzet|first1=Stina|last2=Accetto|first2=Tomaž|last3=Rupnik|first3=Maja|date=2020-10-10|title=Lytic Bacteroides uniformis bacteriophages exhibiting host tropism congruent with diversity generating retroelement|url=http://dx.doi.org/10.1101/2020.10.09.334284|access-date=2020-11-08|doi=10.1101/2020.10.09.334284|s2cid=222349191}} DGRs benefit their host by mutating particular regions of specific target proteins, for instance, phage tail fiber in BPP-1, lipoprotein in legionella pneumophila ( the pathogen behind Legionnaires disease), and TvpA in Treponema denticola (oral-associated periopathogen){{Cite journal|last1=Le Coq|first1=J.|last2=Ghosh|first2=P.|date=2011-08-22|title=Conservation of the C-type lectin fold for massive sequence variation in a Treponema diversity-generating retroelement|journal=Proceedings of the National Academy of Sciences|volume=108|issue=35|pages=14649–14653|doi=10.1073/pnas.1105613108|pmid=21873231|pmc=3167528 |bibcode=2011PNAS..10814649L|issn=0027-8424|doi-access=free}}. An error-prone reverse transcriptase is responsible for generating these hypervariable regions in target proteins (Mutagenic retrohoming). In mutagenic retrohoming, a mutagenized cDNA (containing substantial A to N mutations) is reverse transcribed from a template region (TR), and is replaced with a segment similar to the template region called variable region (VR). Accessory variability determinant (Avd) protein is another component of DGRs, and its complex formation with the error-prone RT is of importance to mutagenic rehoming.{{Cite journal|last1=Alayyoubi|first1=Maher|last2=Guo|first2=Huatao|last3=Dey|first3=Sanghamitra|last4=Golnazarian|first4=Talin|last5=Brooks|first5=Garrett|last6=Rong|first6=Andrew|last7=Miller|first7=Jeffery|last8=Ghosh|first8=Partho|date=2013-02-05|title=Structure of the Essential Diversity-Generating Retroelement Protein bAvd and Its Functionally Important Interaction with Reverse Transcriptase|journal=Structure|volume=21|issue=2|pages=266–276|doi=10.1016/j.str.2012.11.016 |pmid=23273427| pmc=3570691|issn=0969-2126|doi-access=free}}{{Cite journal|last1=Handa|first1=Sumit|last2=Jiang|first2=Yong|last3=Tao|first3=Sijia|last4=Foreman|first4=Robert|last5=Schinazi|first5=Raymond F|last6=Miller|first6=Jeff F|last7=Ghosh|first7=Partho|date=2018-07-11|title=Template-assisted synthesis of adenine-mutagenized cDNA by a retroelement protein complex|journal=Nucleic Acids Research|volume=46|issue=18|pages=9711–9725|doi=10.1093/nar/gky620|pmid=30007279|pmc=6182149|issn=0305-1048|doi-access=free}}
DGRs are beneficial to the evolution and survival of their host. A large fraction of Faecalibacterium prausnitzii phages contain DGRs that are believed to have a role in phage adaptability to the digestive system, as patients with inflammatory bowel disease (IBD), have more phages, but less F.prausnitzii in their stool samples compared to healthy individuals, suggesting that these phages activate during the illness, and that they may trigger F.prausnitzii depletion.{{Cite journal|last1=Cornuault|first1=Jeffrey K.|last2=Petit|first2=Marie-Agnès|last3=Mariadassou|first3=Mahendra|last4=Benevides|first4=Leandro|last5=Moncaut|first5=Elisabeth|last6=Langella|first6=Philippe|last7=Sokol|first7=Harry|last8=De Paepe|first8=Marianne|date=2018-04-03|title=Phages infecting Faecalibacterium prausnitzii belong to novel viral genera that help to decipher intestinal viromes|journal=Microbiome|volume=6|issue=1|page=65|doi=10.1186/s40168-018-0452-1|pmid=29615108|pmc=5883640|issn=2049-2618|doi-access=free}} Several tools have been implemented to identify DGRs, such as DiGReF,{{Cite journal|last1=Schillinger|first1=Thomas|last2=Lisfi|first2=Mohamed|last3=Chi|first3=Jingyun|last4=Cullum|first4=John|last5=Zingler|first5=Nora|date=2012|title=Analysis of a comprehensive dataset of diversity generating retroelements generated by the program DiGReF|journal=BMC Genomics|volume=13|issue=1|pages=430|doi=10.1186/1471-2164-13-430 |pmid=22928525| pmc=3521204|issn=1471-2164|doi-access=free}} DGRscan,{{Cite journal|last=Ye|first=Yuzhen|date=2014-08-15|title=Identification of Diversity-Generating Retroelements in Human Microbiomes|journal=International Journal of Molecular Sciences|volume=15|issue=8|pages=14234–14246|doi=10.3390/ijms150814234|pmid=25196521| pmc=4159848|issn=1422-0067|doi-access=free}} MetaCSST,{{Cite journal|last1=Yan|first1=Fazhe|last2=Yu|first2=Xuelin|last3=Duan|first3=Zhongqu|last4=Lu|first4=Jinyuan|last5=Jia|first5=Ben|last6=Qiao|first6=Yuyang|last7=Sun|first7=Chen|last8=Wei|first8=Chaochun|date=2019-07-19|title=Discovery and characterization of the evolution, variation and functions of diversity-generating retroelements using thousands of genomes and metagenomes|journal=BMC Genomics|volume=20|issue=1|page=595|doi=10.1186/s12864-019-5951-3|pmid=31324156|pmc=6642488|issn=1471-2164|doi-access=free}} and myDGR{{Cite journal|last1=Sharifi|first1=Fatemeh|last2=Ye|first2=Yuzhen|date=2019-05-03|title=MyDGR: a server for identification and characterization of diversity-generating retroelements|journal=Nucleic Acids Research|volume=47|issue=W1|pages=W289–W294|doi=10.1093/nar/gkz329 |pmid=31049585|pmc=6602519|issn=0305-1048|doi-access=free}}