Diversity-generating retroelement

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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

Related Research Articles

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References

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  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.
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  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.
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