Diversity-generating retroelement

From Wikipedia the free encyclopedia

Diversity-generating retroelements (DGRs) are a family of retroelements that were first found in Bordetella phage (BPP-1),[1] and since been found in bacteria (e.g.Treponema denticola[2] and Legionella pneumophila[3]), Archaea, Archaean viruses (e.g. ANMV-1),[4] temperate phages (e.g. Hankyphage[5] and CrAss-like phage[6]), and lytic phages.[7] 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)[8]. 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.[9][10]

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.[11] Several tools have been implemented to identify DGRs, such as DiGReF,[12] DGRscan,[13] MetaCSST,[14] and myDGR[15]

See also[edit]


  1. ^ Doulatov, Sergei; Hodes, Asher; Dai, Lixin; Mandhana, Neeraj; Liu, Minghsun; Deora, Rajendar; Simons, Robert W.; Zimmerly, Steven; Miller, Jeff F. (2004-09-30). "Tropism switching in Bordetella bacteriophage defines a family of diversity-generating retroelements". Nature. 431 (7007): 476–481. Bibcode:2004Natur.431..476D. doi:10.1038/nature02833. ISSN 0028-0836. PMID 15386016. S2CID 1849829.
  2. ^ Nimkulrat, Sutichot; Lee, Heewook; Doak, Thomas G.; Ye, Yuzhen (2016-06-03). "Genomic and Metagenomic Analysis of Diversity-Generating Retroelements Associated with Treponema denticola". Frontiers in Microbiology. 7: 852. doi:10.3389/fmicb.2016.00852. ISSN 1664-302X. PMC 4891356. PMID 27375574.
  3. ^ Arambula, D.; Wong, W.; Medhekar, B. A.; Guo, H.; Gingery, M.; Czornyj, E.; Liu, M.; Dey, S.; Ghosh, P.; Miller, J. F. (2013-04-30). "Surface display of a massively variable lipoprotein by a Legionella diversity-generating retroelement". Proceedings of the National Academy of Sciences. 110 (20): 8212–8217. Bibcode:2013PNAS..110.8212A. doi:10.1073/pnas.1301366110. ISSN 0027-8424. PMC 3657778. PMID 23633572.
  4. ^ Paul, Blair G.; Bagby, Sarah C.; Czornyj, Elizabeth; Arambula, Diego; Handa, Sumit; Sczyrba, Alexander; Ghosh, Partho; Miller, Jeff F.; Valentine, David L. (2015-03-23). "Targeted diversity generation by intraterrestrial archaea and archaeal viruses". Nature Communications. 6 (1): 6585. Bibcode:2015NatCo...6.6585P. doi:10.1038/ncomms7585. ISSN 2041-1723. PMC 4372165. PMID 25798780.
  5. ^ Benler, Sean; Cobián-Güemes, Ana Georgina; McNair, Katelyn; Hung, Shr-Hau; Levi, Kyle; Edwards, Rob; Rohwer, Forest (2018-10-23). "A diversity-generating retroelement encoded by a globally ubiquitous Bacteroides phage". Microbiome. 6 (1): 191. doi:10.1186/s40168-018-0573-6. ISSN 2049-2618. PMC 6199706. PMID 30352623.
  6. ^ Morozova, Vera; Fofanov, Mikhail; Tikunova, Nina; Babkin, Igor; Morozov, Vitaliy V.; Tikunov, Artem (2020-05-22). "First crAss-Like Phage Genome Encoding the Diversity-Generating Retroelement (DGR)". Viruses. 12 (5): 573. doi:10.3390/v12050573. ISSN 1999-4915. PMC 7290462. PMID 32456083.
  7. ^ Hedzet, Stina; Accetto, Tomaž; Rupnik, Maja (2020-10-10). "Lytic Bacteroides uniformis bacteriophages exhibiting host tropism congruent with diversity generating retroelement". doi:10.1101/2020.10.09.334284. S2CID 222349191. Retrieved 2020-11-08. {{cite journal}}: Cite journal requires |journal= (help)
  8. ^ Le Coq, J.; Ghosh, P. (2011-08-22). "Conservation of the C-type lectin fold for massive sequence variation in a Treponema diversity-generating retroelement". Proceedings of the National Academy of Sciences. 108 (35): 14649–14653. Bibcode:2011PNAS..10814649L. doi:10.1073/pnas.1105613108. ISSN 0027-8424. PMC 3167528. PMID 21873231.
  9. ^ Alayyoubi, Maher; Guo, Huatao; Dey, Sanghamitra; Golnazarian, Talin; Brooks, Garrett; Rong, Andrew; Miller, Jeffery; Ghosh, Partho (2013-02-05). "Structure of the Essential Diversity-Generating Retroelement Protein bAvd and Its Functionally Important Interaction with Reverse Transcriptase". Structure. 21 (2): 266–276. doi:10.1016/j.str.2012.11.016. ISSN 0969-2126. PMC 3570691. PMID 23273427.
  10. ^ Handa, Sumit; Jiang, Yong; Tao, Sijia; Foreman, Robert; Schinazi, Raymond F; Miller, Jeff F; Ghosh, Partho (2018-07-11). "Template-assisted synthesis of adenine-mutagenized cDNA by a retroelement protein complex". Nucleic Acids Research. 46 (18): 9711–9725. doi:10.1093/nar/gky620. ISSN 0305-1048. PMC 6182149. PMID 30007279.
  11. ^ Cornuault, Jeffrey K.; Petit, Marie-Agnès; Mariadassou, Mahendra; Benevides, Leandro; Moncaut, Elisabeth; Langella, Philippe; Sokol, Harry; De Paepe, Marianne (2018-04-03). "Phages infecting Faecalibacterium prausnitzii belong to novel viral genera that help to decipher intestinal viromes". Microbiome. 6 (1): 65. doi:10.1186/s40168-018-0452-1. ISSN 2049-2618. PMC 5883640. PMID 29615108.
  12. ^ Schillinger, Thomas; Lisfi, Mohamed; Chi, Jingyun; Cullum, John; Zingler, Nora (2012). "Analysis of a comprehensive dataset of diversity generating retroelements generated by the program DiGReF". BMC Genomics. 13 (1): 430. doi:10.1186/1471-2164-13-430. ISSN 1471-2164. PMC 3521204. PMID 22928525.
  13. ^ Ye, Yuzhen (2014-08-15). "Identification of Diversity-Generating Retroelements in Human Microbiomes". International Journal of Molecular Sciences. 15 (8): 14234–14246. doi:10.3390/ijms150814234. ISSN 1422-0067. PMC 4159848. PMID 25196521.
  14. ^ Yan, Fazhe; Yu, Xuelin; Duan, Zhongqu; Lu, Jinyuan; Jia, Ben; Qiao, Yuyang; Sun, Chen; Wei, Chaochun (2019-07-19). "Discovery and characterization of the evolution, variation and functions of diversity-generating retroelements using thousands of genomes and metagenomes". BMC Genomics. 20 (1): 595. doi:10.1186/s12864-019-5951-3. ISSN 1471-2164. PMC 6642488. PMID 31324156.
  15. ^ Sharifi, Fatemeh; Ye, Yuzhen (2019-05-03). "MyDGR: a server for identification and characterization of diversity-generating retroelements". Nucleic Acids Research. 47 (W1): W289–W294. doi:10.1093/nar/gkz329. ISSN 0305-1048. PMC 6602519. PMID 31049585.