title: A gene transfer agent and a dynamic repertoire of secretion systems hold the keys to the explosive radiation of the emerging pathogen Bartonella.
abstract: Gene transfer agents (GTAs) randomly transfer short fragments of a bacterial genome. A novel putative GTA was recently discovered in the mouse-infecting bacterium Bartonella grahamii. Although GTAs are widespread in phylogenetically diverse bacteria, their role in evolution is largely unknown. Here, we present a comparative analysis of 16 Bartonella genomes ranging from 1.4 to 2.6 Mb in size, including six novel genomes from Bartonella isolated from a cow, two moose, two dogs, and a kangaroo. A phylogenetic tree inferred from 428 orthologous core genes indicates that the deadly human pathogen B. bacilliformis is related to the ruminant-adapted clade, rather than being the earliest diverging species in the genus as previously thought. A gene flux analysis identified 12 genes for a GTA and a phage-derived origin of replication as the most conserved innovations. These are located in a region of a few hundred kb that also contains 8 insertions of gene clusters for type III, IV, and V secretion systems, and genes for putatively secreted molecules such as cholera-like toxins. The phylogenies indicate a recent transfer of seven genes in the virB gene cluster for a type IV secretion system from a cat-adapted B. henselae to a dog-adapted B. vinsonii strain. We show that the B. henselae GTA is functional and can transfer genes in vitro. We suggest that the maintenance of the GTA is driven by selection to increase the likelihood of horizontal gene transfer and argue that this process is beneficial at the population level, by facilitating adaptive evolution of the host-adaptation systems and thereby expansion of the host range size. The process counters gene loss and forces all cells to contribute to the production of the GTA and the secreted molecules. The results advance our understanding of the role that GTAs play for the evolution of bacterial genomes.
authors.affiliation: Department of Molecular Evolution, Cell and Molecular Biology, Science for Life Laboratory, Biomedical Centre, Uppsala University, Uppsala, Sweden.
authors.forename: Lionel
authors.initials: L
authors.lastname: Guy
authors.forename: Björn
authors.initials: B
authors.lastname: Nystedt
authors.forename: Christina
authors.initials: C
authors.lastname: Toft
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Zaremba-Niedzwiedzka
authors.forename: Eva C
authors.initials: EC
authors.lastname: Berglund
authors.forename: Fredrik
authors.initials: F
authors.lastname: Granberg
authors.forename: Kristina
authors.initials: K
authors.lastname: Näslund
authors.forename: Ann-Sofie
authors.initials: AS
authors.lastname: Eriksson
authors.forename: Siv G E
authors.initials: SG
authors.lastname: Andersson
mesh_terms: D000818:Animals; D001473:Bartonella / Q000235:genetics / Q000472:pathogenicity; D005075:Biological Evolution; D002415:Cats; D004285:Dogs; D060733:Electromagnetic Radiation; D022761:Gene Transfer, Horizontal; D016680:Genome, Bacterial; D006801:Humans; D007614:Macropodidae / Q000235:genetics / Q000382:microbiology; D051379:Mice; D005810:Multigene Family; D010802:Phylogeny; D017422:Sequence Analysis, DNA
references.citation: Mol Biol Evol. 2000 Apr;17(4):540-52
references.pmid: 10742046
references.citation: J Bacteriol. 2007 Jul;189(13):4578-86
references.pmid: 17483224
references.citation: Mol Microbiol. 2004 Apr;52(1):81-92
references.pmid: 15049812
references.citation: J Bacteriol. 2005 Feb;187(4):1485-92
references.pmid: 15687213
references.citation: Nat Methods. 2010 Jun;7(6):455-7
references.pmid: 20436475
references.citation: Curr Protoc Bioinformatics. 2003 Feb;Chapter 6:Unit 6.4
references.pmid: 18428704
references.citation: PLoS Pathog. 2006 Nov;2(11):e115
references.pmid: 17121462
references.citation: Gene. 2003 Aug 14;313:103-9
references.pmid: 12957381
references.citation: Bioinformatics. 2008 Dec 1;24(23):2672-6
references.pmid: 18845581
references.citation: Trends Microbiol. 2009 Jun;17(6):226-32
references.pmid: 19464181
references.citation: Int J Med Microbiol. 2002 Feb;291(6-7):555-60
references.pmid: 11890558
references.citation: FEMS Microbiol Rev. 2006 May;30(3):321-81
references.pmid: 16594962
references.citation: Mol Microbiol. 2004 Jul;53(2):541-53
references.pmid: 15228533
references.citation: J Clin Microbiol. 1995 Jan;33(1):154-60
references.pmid: 7699033
references.citation: Nat Genet. 2007 Dec;39(12):1469-76
references.pmid: 18037886
references.citation: Bioinformatics. 2009 Sep 1;25(17):2286-8
references.pmid: 19535536
references.citation: Vet Microbiol. 2009 Mar 2;134(3-4):340-5
references.pmid: 18950961
references.citation: Genome Biol. 2004;5(2):R12
references.pmid: 14759262
references.citation: Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9716-21
references.pmid: 15210978
references.citation: Nature. 2004 Aug 26;430(7003):1024-7
references.pmid: 15329720
references.citation: Appl Environ Microbiol. 2008 Aug;74(16):5224-7
references.pmid: 18567689
references.citation: Bioinformatics. 2009 Apr 1;25(7):962-3
references.pmid: 19254921
references.citation: Nucleic Acids Res. 1997 Mar 1;25(5):955-64
references.pmid: 9023104
references.citation: Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9581-6
references.pmid: 22635269
references.citation: Genome Res. 1998 Mar;8(3):195-202
references.pmid: 9521923
references.citation: Nature. 1998 Nov 12;396(6707):133-40
references.pmid: 9823893
references.citation: Mol Ecol. 2010 Jun;19(11):2241-55
references.pmid: 20465583
references.citation: Anaerobe. 2007 Apr;13(2):43-9
references.pmid: 17513139
references.citation: J Bacteriol. 2005 Sep;187(17):5885-92
references.pmid: 16109929
references.citation: Bioinformatics. 2010 Sep 15;26(18):2334-5
references.pmid: 20624783
references.citation: J Clin Microbiol. 1991 Apr;29(4):830-1
references.pmid: 1716265
references.citation: Emerg Infect Dis. 1998 Apr-Jun;4(2):325-8
references.pmid: 9621208
references.citation: FEMS Microbiol Lett. 2012 Jun;331(1):53-62
references.pmid: 22443140
references.citation: Mol Biol Evol. 2007 Aug;24(8):1586-91
references.pmid: 17483113
references.citation: Mol Microbiol. 2002 Nov;46(4):1053-67
references.pmid: 12421311
references.citation: Bioinformatics. 1999 May;15(5):426-7
references.pmid: 10366664
references.citation: Mol Biol Evol. 2008 Sep;25(9):2069-76
references.pmid: 18635679
references.citation: Appl Environ Microbiol. 2008 May;74(10):2933-9
references.pmid: 18359833
references.citation: Mol Biol Evol. 2008 Feb;25(2):287-300
references.pmid: 18065487
references.citation: Bioinformatics. 2005 May 1;21(9):2104-5
references.pmid: 15647292
references.citation: Cell Microbiol. 2009 Jun;11(6):927-45
references.pmid: 19302579
references.citation: Infect Immun. 2001 Oct;69(10):6495-502
references.pmid: 11553594
references.citation: Vector Borne Zoonotic Dis. 2010 Jun;10(5):429-34
references.pmid: 20017718
references.citation: Nat Rev Genet. 2010 Jul;11(7):465-75
references.pmid: 20517341
references.citation: Nat Rev Microbiol. 2009 Feb;7(2):110-9
references.pmid: 19116615
references.citation: J Mol Biol. 1979 Jun 25;131(2):157-68
references.pmid: 490646
references.citation: Science. 2009 Jan 9;323(5911):272-5
references.pmid: 19131632
references.citation: J Bacteriol. 2006 Nov;188(21):7426-39
references.pmid: 16936024
references.citation: J Struct Biol. 1998;122(1-2):236-46
references.pmid: 9724625
references.citation: Emerg Infect Dis. 2007 Dec;13(12):1961-2
references.pmid: 18258063
references.citation: Cell Microbiol. 2005 May;7(5):687-98
references.pmid: 15839898
references.citation: Mol Biol Evol. 2001 May;18(5):691-9
references.pmid: 11319253
references.citation: Genome Res. 2003 Sep;13(9):2178-89
references.pmid: 12952885
references.citation: Cell Microbiol. 2012 Aug;14(8):1166-73
references.pmid: 22519749
references.citation: PLoS Genet. 2009 Jul;5(7):e1000546
references.pmid: 19578403
references.citation: Mol Biol Evol. 2005 May;22(5):1325-36
references.pmid: 15746011
references.citation: Curr Biol. 2009 Nov 3;19(20):1683-91
references.pmid: 19800234
references.citation: PLoS Pathog. 2010 Jun 10;6(6):e1000946
references.pmid: 20548954
references.citation: PLoS Negl Trop Dis. 2011 Jul;5(7):e1248
references.pmid: 21811647
references.citation: Trends Microbiol. 2007 Feb;15(2):54-62
references.pmid: 17184993
references.citation: Curr Opin Microbiol. 2005 Oct;8(5):579-85
references.pmid: 16099701
references.citation: Int J Syst Evol Microbiol. 2002 Mar;52(Pt 2):383-390
references.pmid: 11931146
references.citation: J Bacteriol. 2007 Oct;189(20):7426-35
references.pmid: 17693516
references.citation: BMC Evol Biol. 2012 May 11;12:65
references.pmid: 22577862
references.citation: Mol Microbiol. 2003 Sep;49(5):1253-66
references.pmid: 12940985
references.citation: Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9722-7
references.pmid: 15210995
references.citation: Proc Biol Sci. 2001 Jan 7;268(1462):61-9
references.pmid: 12123299
references.citation: Bioinformatics. 2003 Aug 12;19(12):1572-4
references.pmid: 12912839
references.citation: Microbiol Mol Biol Rev. 2004 Dec;68(4):692-744
references.pmid: 15590781
references.citation: Future Microbiol. 2009 Aug;4(6):743-58
references.pmid: 19659429
references.citation: Bioinformatics. 2006 Nov 1;22(21):2688-90
references.pmid: 16928733
references.citation: Nucleic Acids Res. 1997 Sep 1;25(17):3389-402
references.pmid: 9254694
references.citation: PLoS Genet. 2009 Jan;5(1):e1000344
references.pmid: 19165319
references.citation: Nucleic Acids Res. 2002 Apr 1;30(7):1575-84
references.pmid: 11917018
references.citation: Plasmid. 2003 Jan;49(1):44-52
references.pmid: 12584000
references.citation: J Clin Microbiol. 1991 Jul;29(7):1299-302
references.pmid: 1715879
references.citation: BMC Bioinformatics. 2010 Mar 08;11:119
references.pmid: 20211023
references.citation: Trends Ecol Evol. 2007 Dec;22(12):643-51
references.pmid: 17981363
references.citation: J Exp Med. 2004 Nov 15;200(10):1267-78
references.pmid: 15534369
references.citation: PLoS Genet. 2011 Feb 10;7(2):e1001296
references.pmid: 21347280
references.citation: Gene. 2003 Jul 17;312:151-63
references.pmid: 12909351
references.citation: Proc Natl Acad Sci U S A. 1974 Mar;71(3):971-3
references.pmid: 4522805
references.citation: Brief Bioinform. 2008 Jul;9(4):286-98
references.pmid: 18372315
references.citation: Science. 1968 Dec 13;162(3859):1243-8
references.pmid: 5699198
references.citation: Nature. 2007 Nov 15;450(7168):411-4
references.pmid: 18004383
references.citation: J Theor Biol. 2005 Oct 21;236(4):392-6
references.pmid: 15899500
references.citation: Nucleic Acids Res. 2007;35(9):3100-8
references.pmid: 17452365