title: Pervasive domestication of defective prophages by bacteria.
abstract: Integrated phages (prophages) are major contributors to the diversity of bacterial gene repertoires. Domestication of their components is thought to have endowed bacteria with molecular systems involved in secretion, defense, warfare, and gene transfer. However, the rates and mechanisms of domestication remain unknown. We used comparative genomics to study the evolution of prophages within the bacterial genome. We identified over 300 vertically inherited prophages within enterobacterial genomes. Some of these elements are very old and might predate the split between Escherichia coli and Salmonella enterica. The size distribution of prophage elements is bimodal, suggestive of rapid prophage inactivation followed by much slower genetic degradation. Accordingly, we observed a pervasive pattern of systematic counterselection of nonsynonymous mutations in prophage genes. Importantly, such patterns of purifying selection are observed not only on accessory regions but also in core phage genes, such as those encoding structural and lysis components. This suggests that bacterial hosts select for phage-associated functions. Several of these conserved prophages have gene repertoires compatible with described functions of adaptive prophage-derived elements such as bacteriocins, killer particles, gene transfer agents, or satellite prophages. We suggest that bacteria frequently domesticate their prophages. Most such domesticated elements end up deleted from the bacterial genome because they are replaced by analogous functions carried by new prophages. This puts the bacterial genome in a state of continuous flux of acquisition and loss of phage-derived adaptive genes.
authors.affiliation: Microbial Evolutionary Genomics, Institut Pasteur, 75724 Paris, France;CNRS, UMR 3525, 75724 Paris, France; andSorbonne Universités, UPMC, Université Paris 6, IFD, 75252 Paris Cedex 05, France lbobay@pasteur.fr.
authors.forename: Louis-Marie
authors.initials: LM
authors.lastname: Bobay
authors.affiliation: Microbial Evolutionary Genomics, Institut Pasteur, 75724 Paris, France;CNRS, UMR 3525, 75724 Paris, France; and.
authors.forename: Marie
authors.initials: M
authors.lastname: Touchon
authors.affiliation: Microbial Evolutionary Genomics, Institut Pasteur, 75724 Paris, France;CNRS, UMR 3525, 75724 Paris, France; and.
authors.forename: Eduardo P C
authors.initials: EP
authors.lastname: Rocha
mesh_terms: D004926:Escherichia coli / Q000821:virology*; D039002:Prophages / Q000502:physiology*; D019779:Salmonella enterica / Q000821:virology*
keywords: prokaryotes; viruses
references.citation: Biochimie. 2002 May-Jun;84(5-6):499-510
references.pmid: 12423794
references.citation: ISME J. 2011 Apr;5(4):613-26
references.pmid: 20962878
references.citation: Genome Res. 2004 Jun;14(6):1036-42
references.pmid: 15173110
references.citation: ISME J. 2011 Sep;5(9):1451-60
references.pmid: 21412345
references.citation: Proc Natl Acad Sci U S A. 2013 Jun 25;110(26):10771-6
references.pmid: 23690590
references.citation: Chem Immunol Allergy. 2007;93:42-57
references.pmid: 17369699
references.citation: BMC Bioinformatics. 2010 Jun 15;11:324
references.pmid: 20550700
references.citation: Mol Microbiol. 2004 Jul;53(1):9-18
references.pmid: 15225299
references.citation: Res Microbiol. 2007 May;158(4):311-7
references.pmid: 17490863
references.citation: J Virol. 1975 May;15(5):1231-8
references.pmid: 16789156
references.citation: J Bacteriol. 2004 Aug;186(15):5116-28
references.pmid: 15262948
references.citation: Proc Biol Sci. 2007 Aug 22;274(1621):1921-9
references.pmid: 17535798
references.citation: Science. 2014 Jan 31;343(6170):529-33
references.pmid: 24407482
references.citation: Nat Rev Microbiol. 2012 Jun 11;10(7):472-82
references.pmid: 22683880
references.citation: Virology. 1970 Mar;40(3):673-84
references.pmid: 4908733
references.citation: Mol Gen Genet. 1972;119(1):75-88
references.pmid: 4564719
references.citation: Cell. 2012 Aug 17;150(4):792-802
references.pmid: 22901809
references.citation: J Mol Biol. 2006 Jun 2;359(2):496-507
references.pmid: 16631788
references.citation: PLoS Genet. 2013 Jun;9(6):e1003539
references.pmid: 23754962
references.citation: J Mol Biol. 1972 Nov 14;71(2):433-48
references.pmid: 4564486
references.citation: J Cell Physiol. 1970 Dec;76(3):253-63
references.pmid: 5502350
references.citation: J Bacteriol. 2003 Nov;185(21):6467-71
references.pmid: 14563883
references.citation: Bacteriol Rev. 1975 Dec;39(4):464-515
references.pmid: 1108869
references.citation: PLoS Genet. 2014 Mar 06;10(3):e1004181
references.pmid: 24603854
references.citation: Virology. 2012 Oct 25;432(2):277-82
references.pmid: 22709958
references.citation: Bioinformatics. 2010 Oct 1;26(19):2462-3
references.pmid: 20798170
references.citation: Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3801-6
references.pmid: 10097118
references.citation: J Theor Biol. 2006 Mar 21;239(2):226-35
references.pmid: 16239014
references.citation: Nature. 1999 Jun 10;399(6736):541-8
references.pmid: 10376593
references.citation: Virology. 1998 Nov 10;251(1):49-58
references.pmid: 9813202
references.citation: Trends Microbiol. 2007 Feb;15(2):54-62
references.pmid: 17184993
references.citation: Curr Biol. 2006 Oct 24;16(20):2048-52
references.pmid: 17055985
references.citation: Bacteriol Rev. 1967 Dec;31(4):230-314
references.pmid: 4865539
references.citation: J Mol Biol. 1992 Oct 20;227(4):1086-99
references.pmid: 1433288
references.citation: Trends Microbiol. 2001 Nov;9(11):535-40
references.pmid: 11825713
references.citation: Nucleic Acids Res. 2006;34(20):5839-51
references.pmid: 17062630
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4154-9
references.pmid: 19251641
references.citation: Virology. 1974 Jun;59(2):532-44
references.pmid: 4598709
references.citation: Virology. 2012 Dec 20;434(2):210-21
references.pmid: 23131350
references.citation: Adv Virus Res. 2012;83:219-98
references.pmid: 22748812
references.citation: Nat Rev Microbiol. 2011 Aug 12;9(9):647-57
references.pmid: 21836625
references.citation: PLoS Genet. 2010 Aug 05;6(8):
references.pmid: 20700439
references.citation: Genetics. 2006 Apr;172(4):2665-81
references.pmid: 16489234
references.citation: J Bacteriol. 2002 Aug;184(16):4529-35
references.pmid: 12142423
references.citation: PLoS Pathog. 2009 May;5(5):e1000408
references.pmid: 19412337
references.citation: Infect Immun. 2001 Oct;69(10):6186-92
references.pmid: 11553559
references.citation: J Virol. 1977 Feb;21(2):560-4
references.pmid: 319256
references.citation: Mol Microbiol. 2003 Jul;49(2):277-300
references.pmid: 12886937
references.citation: Nat Commun. 2010;1:147
references.pmid: 21266997
references.citation: J Mol Biol. 1968 Feb 14;31(3):487-505
references.pmid: 5637199
references.citation: PLoS One. 2012;7(8):e42639
references.pmid: 22880062
references.citation: Science. 2013 Oct 4;342(6154):104-8
references.pmid: 24092741
references.citation: Curr Opin Microbiol. 2005 Aug;8(4):459-65
references.pmid: 15979389
references.citation: J Bacteriol. 1990 May;172(5):2667-74
references.pmid: 2110147
references.citation: Mol Microbiol. 2009 Apr;72(1):98-108
references.pmid: 19347993
references.citation: Mol Biol Evol. 2013 Apr;30(4):737-51
references.pmid: 23243039
references.citation: PLoS One. 2013;8(3):e59043
references.pmid: 23536852