title: A bioinformatic analysis of ribonucleotide reductase genes in phage genomes and metagenomes.
abstract: BACKGROUND
  Ribonucleotide reductase (RNR), the enzyme responsible for the formation of deoxyribonucleotides from ribonucleotides, is found in all domains of life and many viral genomes. RNRs are also amongst the most abundant genes identified in environmental metagenomes. This study focused on understanding the distribution, diversity, and evolution of RNRs in phages (viruses that infect bacteria). Hidden Markov Model profiles were used to analyze the proteins encoded by 685 completely sequenced double-stranded DNA phages and 22 environmental viral metagenomes to identify RNR homologs in cultured phages and uncultured viral communities, respectively.
  
  
  RESULTS
  RNRs were identified in 128 phage genomes, nearly tripling the number of phages known to encode RNRs. Class I RNR was the most common RNR class observed in phages (70%), followed by class II (29%) and class III (28%). Twenty-eight percent of the phages contained genes belonging to multiple RNR classes. RNR class distribution varied according to phage type, isolation environment, and the host's ability to utilize oxygen. The majority of the phages containing RNRs are Myoviridae (65%), followed by Siphoviridae (30%) and Podoviridae (3%). The phylogeny and genomic organization of phage and host RNRs reveal several distinct evolutionary scenarios involving horizontal gene transfer, co-evolution, and differential selection pressure. Several putative split RNR genes interrupted by self-splicing introns or inteins were identified, providing further evidence for the role of frequent genetic exchange. Finally, viral metagenomic data indicate that RNRs are prevalent and highly dynamic in uncultured viral communities, necessitating future research to determine the environmental conditions under which RNRs provide a selective advantage.
  
  
  CONCLUSIONS
  This comprehensive study describes the distribution, diversity, and evolution of RNRs in phage genomes and environmental viral metagenomes. The distinct distributions of specific RNR classes amongst phages, combined with the various evolutionary scenarios predicted from RNR phylogenies suggest multiple inheritance sources and different selective forces for RNRs in phages. This study significantly improves our understanding of phage RNRs, providing insight into the diversity and evolution of this important auxiliary metabolic gene as well as the evolution of phages in response to their bacterial hosts and environments.
authors: College of Marine Science, University of South Florida, St, Petersburg, FL 33701, USA.
authors: Bhakti
authors: B
authors: Dwivedi
authors: Bingjie
authors: B
authors: Xue
authors: Daniel
authors: D
authors: Lundin
authors: Robert A
authors: RA
authors: Edwards
authors: Mya
authors: M
authors: Breitbart
mesh_terms: D001419:Bacteria / Q000821:virology; D001435:Bacteriophages / Q000145:classification / Q000201:enzymology* / Q000235:genetics; D001483:Base Sequence; D030541:Databases, Genetic; D019143:Evolution, Molecular; D022761:Gene Transfer, Horizontal; D016679:Genome, Viral; D023281:Genomics; D054892:Metagenome; D010802:Phylogeny; D012264:Ribonucleotide Reductases / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D014764:Viral Proteins; D012264:Ribonucleotide Reductases
references: PLoS Comput Biol. 2010 Feb 26;6(2):e1000667
references: 20195499
references: Proc Biol Sci. 2004 Mar 22;271(1539):565-74
references: 15156913
references: Genes Dev. 2002 Feb 1;16(3):351-62
references: 11825876
references: Microbiology (Reading). 2002 Apr;148(Pt 4):985-1001
references: 11932445
references: Res Microbiol. 2004 Nov;155(9):720-5
references: 15501648
references: Syst Biol. 2007 Aug;56(4):564-77
references: 17654362
references: Mol Biol Evol. 2000 Apr;17(4):540-52
references: 10742046
references: Regul Toxicol Pharmacol. 2005 Dec;43(3):301-12
references: 16188359
references: Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14250-5
references: 12384570
references: Appl Environ Microbiol. 2005 Mar;71(3):1598-609
references: 15746365
references: Cell. 1986 Oct 10;47(1):81-7
references: 3757035
references: ISME J. 2008 Nov;2(11):1112-21
references: 18719614
references: Environ Microbiol. 2009 Nov;11(11):2935-51
references: 19840100
references: Appl Environ Microbiol. 2010 Apr;76(8):2673-7
references: 20154108
references: J Mol Biol. 2007 May 11;368(4):966-81
references: 17383677
references: Environ Microbiol. 2008 Sep;10(9):2277-86
references: 18479440
references: Proc Natl Acad Sci U S A. 2005 Nov 29;102(48):17472-7
references: 16287978
references: Environ Microbiol. 2007 Jul;9(7):1675-95
references: 17564603
references: Microbiology (Reading). 1995 Sep;141 ( Pt 9):2183-90
references: 7496530
references: Environ Microbiol. 2012 Feb;14(2):540-58
references: 22188618
references: J Bacteriol. 2007 May;189(9):3655-9
references: 17307844
references: J Bacteriol. 1984 Jan;157(1):247-52
references: 6360998
references: Appl Environ Microbiol. 2007 Dec;73(23):7629-41
references: 17921274
references: Environ Microbiol. 2009 Sep;11(9):2370-87
references: 19508343
references: Trends Microbiol. 2010 Jan;18(1):20-9
references: 19896852
references: BMC Evol Biol. 2010 Dec 10;10:383
references: 21143941
references: Appl Environ Microbiol. 2007 Nov;73(21):7059-66
references: 17827313
references: Virol J. 2012 Jan 27;9:35
references: 22284308
references: Microbiol Mol Biol Rev. 2000 Mar;64(1):69-114
references: 10704475
references: Nucleic Acids Res. 2011 Jan;39(Database issue):D225-9
references: 21109532
references: Science. 2004 Jul 9;305(5681):245-8
references: 15247479
references: Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W289-94
references: 15980472
references: PLoS One. 2008 Sep 23;3(9):e3263
references: 18810270
references: Appl Environ Microbiol. 2011 Nov;77(21):7663-8
references: 21926223
references: Nucleic Acids Res. 1994 Sep 11;22(18):3715-21
references: 7937082
references: Appl Environ Microbiol. 2010 Oct;76(20):6843-52
references: 20802084
references: PLoS One. 2008 Aug 22;3(8):e3042
references: 18725995
references: Appl Environ Microbiol. 2008 Oct;74(19):5975-85
references: 18708511
references: EMBO J. 1986 Aug;5(8):2031-6
references: 3530746
references: Nucleic Acids Res. 2011 Jul;39(Web Server issue):W29-37
references: 21593126
references: Environ Microbiol. 2009 Nov;11(11):2806-20
references: 19555373
references: Nature. 2008 Mar 20;452(7185):340-3
references: 18311127
references: Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1692-7
references: 9465078
references: PLoS Biol. 2005 May;3(5):e144
references: 15828858
references: J Bacteriol. 2007 Feb;189(3):980-90
references: 17122344
references: Nat Biotechnol. 2008 Oct;26(10):1135-45
references: 18846087
references: Bioinformatics. 2005 May 1;21(9):2104-5
references: 15647292
references: Environ Microbiol. 2010 Nov;12(11):3035-56
references: 20662890
references: Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6176-81
references: 17395719
references: J Mol Biol. 2006 Dec 8;364(4):667-77
references: 17027029
references: Genome Res. 2008 Feb;18(2):293-7
references: 18077539
references: Mol Biol Evol. 2011 Oct;28(10):2731-9
references: 21546353
references: J Bacteriol. 2008 Sep;190(17):5753-65
references: 18567664
references: Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1356-7
references: 9465018
references: J Biol Chem. 1997 Jul 18;272(29):18044-50
references: 9218434
references: Curr Opin Virol. 2011 Oct;1(4):289-97
references: 22440785
references: Environ Microbiol. 2011 Aug;13(8):1956-72
references: 20738373
references: Appl Environ Microbiol. 2008 Sep;74(17):5317-24
references: 18586962
references: Annu Rev Biochem. 1998;67:71-98
references: 9759483
references: Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1358-62
references: 1741388
references: Nucleic Acids Res. 2009 May;37(8):2560-73
references: 19264795
references: FEMS Microbiol Ecol. 2011 Jul;77(1):120-33
references: 21410492
references: Microbiol Mol Biol Rev. 2003 Mar;67(1):86-156, table of contents
references: 12626685
references: Nature. 2005 Nov 3;438(7064):86-9
references: 16222247
references: Syst Biol. 2003 Oct;52(5):696-704
references: 14530136
references: BMC Genomics. 2006 Jan 18;7:8
references: 16417644
references: Mol Microbiol. 1996 Mar;19(6):1343-55
references: 8730875
references: Appl Environ Microbiol. 2011 Feb;77(4):1284-91
references: 21183634
references: ISME J. 2010 Jun;4(6):739-51
references: 20147985
references: Environ Microbiol. 2004 Jan;6(1):1-11
references: 14686936
references: J Bacteriol. 2000 Oct;182(19):5281-9
references: 10986228
references: Annu Rev Biochem. 2006;75:681-706
references: 16756507
references: Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11669-73
references: 7972121
references: J Mol Evol. 2002 Aug;55(2):138-52
references: 12107591
references: PLoS Biol. 2006 Jul;4(8):e234
references: 16802857
references: Nucleic Acids Res. 2010 Nov;38(20):e191
references: 20805240
references: J Bacteriol. 2003 Sep;185(17):5220-33
references: 12923095
references: Environ Microbiol. 2010 Nov;12(11):2965-76
references: 20561021
references: Environ Microbiol. 2009 Aug;11(8):2055-64
references: 19689706
references: Nature. 2007 Sep 6;449(7158):83-6
references: 17805294
references: J Biol Chem. 2009 Oct 30;284(44):29997-30003
references: 19710025
references: Int J Syst Bacteriol. 1991 Apr;41(2):240-6
references: 1713054
references: J Biol Chem. 1994 Aug 12;269(32):20229-32
references: 8051113
references: Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18413-8
references: 19017800
references: J Bacteriol. 2001 Dec;183(24):7260-72
references: 11717286
references: Nucleic Acids Res. 2010 Jul;38(13):4207-17
references: 20215432
references: Nucleic Acids Res. 2002 May 1;30(9):1935-43
references: 11972330
references: BMC Genomics. 2010 Mar 30;11:214
references: 20353581
references: Science. 2009 Nov 6;326(5954):858-61
references: 19892985
references: J Biol Chem. 2001 Sep 21;276(38):35836-41
references: 11441020
references: Virology. 2008 Sep 1;378(2):226-32
references: 18599103
references: PLoS Biol. 2006 Nov;4(11):e368
references: 17090214
references: Arch Virol. 2012 Feb;157(2):391-5
references: 22116495
references: BMC Genomics. 2009 Dec 08;10:589
references: 19995434
references: Microbiol Immunol. 1992;36(1):93-7
references: 1584076
references: Appl Environ Microbiol. 2002 May;68(5):2589-94
references: 11976141
references: Microbiology (Reading). 2003 Apr;149(Pt 4):1011-1020
references: 12686643
references: J Bacteriol. 2010 Oct;192(20):5441-53
references: 20709901
references: Environ Microbiol. 2007 Jul;9(7):1711-23
references: 17564605
references: Nucleic Acids Res. 2005 Oct 27;33(19):6203-13
references: 16257983
references: Proc Natl Acad Sci U S A. 2011 Sep 27;108(39):E757-64
references: 21844365
references: Nucleic Acids Res. 2002 Jan 1;30(1):383-4
references: 11752343
references: Virus Genes. 1995;11(2-3):285-97
references: 8828153
references: Appl Environ Microbiol. 2011 Nov;77(21):7730-9
references: 21926220
references: J Bacteriol. 2005 May;187(9):3188-200
references: 15838046
references: Proc Natl Acad Sci U S A. 1984 May;81(10):3049-53
references: 6328492