title: Motif depletion in bacteriophages infecting hosts with CRISPR systems.
abstract: BACKGROUND
  CRISPR is a microbial immune system likely to be involved in host-parasite coevolution. It functions using target sequences encoded by the bacterial genome, which interfere with invading nucleic acids using a homology-dependent system. The system also requires protospacer associated motifs (PAMs), short motifs close to the target sequence that are required for interference in CRISPR types I and II. Here, we investigate whether PAMs are depleted in phage genomes due to selection pressure to escape recognition.
  
  
  RESULTS
  To this end, we analyzed two data sets. Phages infecting all bacterial hosts were analyzed first, followed by a detailed analysis of phages infecting the genus Streptococcus, where PAMs are best understood. We use two different measures of motif underrepresentation that control for codon bias and the frequency of submotifs. We compare phages infecting species with a particular CRISPR type to those infecting species without that type. Since only known PAMs were investigated, the analysis is restricted to CRISPR types I-C and I-E and in Streptococcus to types I-C and II. We found evidence for PAM depletion in Streptococcus phages infecting hosts with CRISPR type I-C, in Vibrio phages infecting hosts with CRISPR type I-E and in Streptococcus thermopilus phages infecting hosts with type II-A, known as CRISPR3.
  
  
  CONCLUSIONS
  The observed motif depletion in phages with hosts having CRISPR can be attributed to selection rather than to mutational bias, as mutational bias should affect the phages of all hosts. This observation implies that the CRISPR system has been efficient in the groups discussed here.
authors.affiliation: IST Austria, Am Campus 1, 3400 Klosterneuburg, Austria. akupczok@ifam.uni-kiel.de.
authors.forename: Anne
authors.initials: A
authors.lastname: Kupczok
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Bollback
mesh_terms: D001419:Bacteria / Q000235:genetics* / Q000821:virology*; D001435:Bacteriophages / Q000235:genetics*; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D054884:Host-Pathogen Interactions; D059372:Nucleotide Motifs; D013291:Streptococcus / Q000235:genetics / Q000821:virology
references.citation: Microbiology (Reading). 2009 Mar;155(Pt 3):733-740
references.pmid: 19246744
references.citation: RNA Biol. 2013 May;10(5):738-48
references.pmid: 23392249
references.citation: J Bacteriol. 2005 Dec;187(24):8370-4
references.pmid: 16321941
references.citation: Mol Microbiol. 2012 Sep;85(6):1057-71
references.pmid: 22834929
references.citation: Mol Microbiol. 2011 Jan;79(1):35-49
references.pmid: 21166892
references.citation: Appl Environ Microbiol. 2011 Jun;77(11):3819-29
references.pmid: 21460108
references.citation: Nucleic Acids Res. 2011 Nov;39(21):9275-82
references.pmid: 21813460
references.citation: Microbiology (Reading). 2011 Feb;157(2):430-437
references.pmid: 28206903
references.citation: J Biol Chem. 2012 Sep 28;287(40):33351-63
references.pmid: 22767603
references.citation: Nucleic Acids Res. 2005 Jan 13;33(1):e6
references.pmid: 15653627
references.citation: Genome Res. 2003 Feb;13(2):145-58
references.pmid: 12566393
references.citation: Int J Food Microbiol. 2009 Apr 30;131(1):62-70
references.pmid: 18635282
references.citation: PLoS One. 2012;7(4):e35888
references.pmid: 22558257
references.citation: BMC Microbiol. 2012 Dec 21;12:301
references.pmid: 23259527
references.citation: Genome Res. 2001 Jun;11(6):946-58
references.pmid: 11381024
references.citation: J Bacteriol. 2008 Feb;190(4):1390-400
references.pmid: 18065545
references.citation: RNA Biol. 2013 May;10(5):716-25
references.pmid: 23619643
references.citation: Microbiology (Reading). 2009 Jun;155(Pt 6):1966-1976
references.pmid: 19383692
references.citation: Mol Biol Evol. 2013 Apr;30(4):772-80
references.pmid: 23329690
references.citation: Nucleic Acids Res. 2011 Jul;39(Web Server issue):W347-52
references.pmid: 21672955
references.citation: Genome Biol. 2007;8(5):R71
references.pmid: 17475002
references.citation: J Bacteriol. 2008 Feb;190(4):1401-12
references.pmid: 18065539
references.citation: J Comput Biol. 1996 Fall;3(3):345-60
references.pmid: 8891954
references.citation: Annu Rev Genet. 2012;46:311-39
references.pmid: 23145983
references.citation: Trends Genet. 2000 Jun;16(6):276-7
references.pmid: 10827456
references.citation: Appl Environ Microbiol. 2012 Aug;78(15):5353-60
references.pmid: 22636003
references.citation: PLoS Genet. 2013 Apr;9(4):e1003454
references.pmid: 23637624
references.citation: Nucleic Acids Res. 2011 Jul;39(Web Server issue):W29-37
references.pmid: 21593126
references.citation: Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10098-103
references.pmid: 21646539
references.citation: Nature. 2013 Jan 17;493(7432):429-32
references.pmid: 23242138
references.citation: Nucleic Acids Res. 2007 Jul;35(Web Server issue):W52-7
references.pmid: 17537822
references.citation: Science. 2007 Mar 23;315(5819):1709-12
references.pmid: 17379808
references.citation: RNA Biol. 2013 May;10(5):891-9
references.pmid: 23403393
references.citation: Curr Opin Microbiol. 1998 Oct;1(5):598-610
references.pmid: 10066522
references.citation: Mol Cell. 2012 Jun 8;46(5):606-15
references.pmid: 22521690
references.citation: Mol Biol Evol. 2003 Jun;20(6):901-6
references.pmid: 12716998
references.citation: Proc Natl Acad Sci U S A. 2013 Aug 27;110(35):14396-401
references.pmid: 23940313
references.citation: Trends Genet. 1995 Jul;11(7):283-90
references.pmid: 7482779
references.citation: Environ Microbiol. 2004 Sep;6(9):938-47
references.pmid: 15305919
references.citation: PLoS One. 2012;7(11):e50797
references.pmid: 23189210
references.citation: Mol Cell. 2012 Jun 8;46(5):595-605
references.pmid: 22521689
references.citation: Syst Biol. 2003 Oct;52(5):696-704
references.pmid: 14530136
references.citation: Genome Res. 2004 Jun;14(6):1188-90
references.pmid: 15173120
references.citation: BMC Genomics. 2006 Jan 18;7:8
references.pmid: 16417644
references.citation: PLoS Genet. 2013;9(3):e1003312
references.pmid: 23516369
references.citation: PLoS Genet. 2013;9(9):e1003844
references.pmid: 24086164
references.citation: Nucleic Acids Res. 1992 Mar 25;20(6):1363-70
references.pmid: 1313968
references.citation: PLoS One. 2012;7(1):e30288
references.pmid: 22272325
references.citation: Nucleic Acids Res. 2014 Feb;42(4):2577-90
references.pmid: 24270795
references.citation: Nat Commun. 2012 Jul 10;3:945
references.pmid: 22781758
references.citation: J Virol. 1994 May;68(5):2889-97
references.pmid: 8151759
references.citation: Nat Rev Microbiol. 2011 Jun;9(6):467-77
references.pmid: 21552286
references.citation: Nat Methods. 2007 Jan;4(1):63-72
references.pmid: 17179938
references.citation: PLoS Pathog. 2008 Jun 06;4(6):e1000079
references.pmid: 18535658
references.citation: Annu Rev Biochem. 2013;82:237-66
references.pmid: 23495939
references.citation: BMC Genomics. 2012 Oct 05;13:533
references.pmid: 23035691