title: Structural alterations in a component of cytochrome c oxidase and molecular evolution of pathogenic Neisseria in humans.
abstract: Three closely related bacterial species within the genus Neisseria are of importance to human disease and health. Neisseria meningitidis is a major cause of meningitis, while Neisseria gonorrhoeae is the agent of the sexually transmitted disease gonorrhea and Neisseria lactamica is a common, harmless commensal of children. Comparative genomics have yet to yield clear insights into which factors dictate the unique host-parasite relationships exhibited by each since, as a group, they display remarkable conservation at the levels of nucleotide sequence, gene content and synteny. Here, we discovered two rare alterations in the gene encoding the CcoP protein component of cytochrome cbb(3) oxidase that are phylogenetically informative. One is a single nucleotide polymorphism resulting in CcoP truncation that acts as a molecular signature for the species N. meningitidis. We go on to show that the ancestral ccoP gene arose by a unique gene duplication and fusion event and is specifically and completely distributed within species of the genus Neisseria. Surprisingly, we found that strains engineered to express either of the two CcoP forms conditionally differed in their capacity to support nitrite-dependent, microaerobic growth mediated by NirK, a nitrite reductase. Thus, we propose that changes in CcoP domain architecture and ensuing alterations in function are key traits in successive, adaptive radiations within these metapopulations. These findings provide a dramatic example of how rare changes in core metabolic proteins can be connected to significant macroevolutionary shifts. They also show how evolutionary change at the molecular level can be linked to metabolic innovation and its reversal as well as demonstrating how genotype can be used to infer alterations of the fitness landscape within a single host.
authors.affiliation: Department of Molecular Biosciences, University of Oslo, Oslo, Norway.
authors.forename: Marina
authors.initials: M
authors.lastname: Aspholm
authors.forename: Finn Erik
authors.initials: FE
authors.lastname: Aas
authors.forename: Odile B
authors.initials: OB
authors.lastname: Harrison
authors.forename: Diana
authors.initials: D
authors.lastname: Quinn
authors.forename: Ashild
authors.initials: A
authors.lastname: Vik
authors.forename: Raimonda
authors.initials: R
authors.lastname: Viburiene
authors.forename: Tone
authors.initials: T
authors.lastname: Tønjum
authors.forename: James
authors.initials: J
authors.lastname: Moir
authors.forename: Martin C J
authors.initials: MC
authors.lastname: Maiden
authors.forename: Michael
authors.initials: M
authors.lastname: Koomey
mesh_terms: D001483:Base Sequence; D003576:Electron Transport Complex IV / Q000737:chemistry / Q000235:genetics*; D019143:Evolution, Molecular; D005838:Genotype; D006790:Host-Parasite Interactions / Q000235:genetics*; D006801:Humans; D015151:Immunoblotting; D008969:Molecular Sequence Data; D009343:Neisseria / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide
chemical_list: D003576:Electron Transport Complex IV
references.citation: Genome Biol. 2008;9(3):R60
references.pmid: 18366792
references.citation: J Clin Microbiol. 2004 Nov;42(11):5146-53
references.pmid: 15528708
references.citation: Genetics. 2007 Mar;175(3):1251-66
references.pmid: 17151252
references.citation: Lancet. 1991 Mar 2;337(8740):514-7
references.pmid: 1705642
references.citation: Mol Microbiol. 2005 Nov;58(3):800-9
references.pmid: 16238628
references.citation: Microbiology (Reading). 2008 Sep;154(Pt 9):2857-2864
references.pmid: 18757819
references.citation: Biochim Biophys Acta. 1998 Jul 20;1365(3):421-34
references.pmid: 9711295
references.citation: J Bacteriol. 2008 Apr;190(7):2488-95
references.pmid: 18245279
references.citation: BMC Biol. 2007 Sep 07;5:35
references.pmid: 17825091
references.citation: J Biol Chem. 2006 Nov 3;281(44):33115-26
references.pmid: 16954205
references.citation: Biochem Biophys Res Commun. 2009 Jan 2;378(1):84-9
references.pmid: 19013435
references.citation: J Bacteriol. 2008 Jan;190(1):387-400
references.pmid: 17951381
references.citation: Mol Gen Genet. 1996 Jul 19;251(5):509-17
references.pmid: 8709956
references.citation: Microbiology (Reading). 2008 Jan;154(Pt 1):226-239
references.pmid: 18174141
references.citation: J Bacteriol. 2002 Jun;184(11):2987-93
references.pmid: 12003939
references.citation: IUBMB Life. 2008 Sep;60(9):629-36
references.pmid: 18618739
references.citation: J Bacteriol. 2007 Feb;189(3):1138-44
references.pmid: 17122348
references.citation: Science. 2008 Apr 11;320(5873):237-9
references.pmid: 18403712
references.citation: J Biol Inorg Chem. 2007 Nov;12(8):1119-27
references.pmid: 17712582
references.citation: Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3140-5
references.pmid: 9501229
references.citation: Infect Genet Evol. 2008 Sep;8(5):558-65
references.pmid: 18479979
references.citation: Chem Rev. 1996 Nov 7;96(7):2889-2908
references.pmid: 11848844
references.citation: Curr Opin Microbiol. 2008 Oct;11(5):467-71
references.pmid: 18822386
references.citation: Mol Microbiol. 2009 Jan;71(1):227-39
references.pmid: 19007408
references.citation: Curr Biol. 1993 Sep 1;3(9):567-72
references.pmid: 15335669
references.citation: Biochem Soc Trans. 2006 Feb;34(Pt 1):139-42
references.pmid: 16417504
references.citation: Trends Ecol Evol. 2000 Nov 1;15(11):454-459
references.pmid: 11050348
references.citation: Mol Microbiol. 2007 Aug;65(3):607-24
references.pmid: 17608667
references.citation: Infect Immun. 2000 Sep;68(9):5241-6
references.pmid: 10948150
references.citation: Infect Immun. 2007 Mar;75(3):1534-6
references.pmid: 17220319
references.citation: Mol Microbiol. 1997 Feb;23(4):799-812
references.pmid: 9157250
references.citation: Microbiology (Reading). 2002 Jun;148(Pt 6):1813-1819
references.pmid: 12055301
references.citation: J Biol Chem. 2002 Aug 30;277(35):31474-83
references.pmid: 12070166
references.citation: Biochim Biophys Acta. 2004 Apr 12;1655(1-3):388-99
references.pmid: 15100055
references.citation: Microbiology (Reading). 2005 Sep;151(Pt 9):2907-2922
references.pmid: 16151203
references.citation: EMBO J. 2000 Dec 1;19(23):6408-18
references.pmid: 11101514
references.citation: Proc Natl Acad Sci U S A. 2005 May 3;102(18):6379-84
references.pmid: 15851671
references.citation: J Biol Chem. 2009 Apr 24;284(17):11301-8
references.pmid: 19252222
references.citation: PLoS Comput Biol. 2009 Aug;5(8):e1000455
references.pmid: 19662158
references.citation: FEMS Microbiol Lett. 2009 Dec;301(2):232-40
references.pmid: 19889029
references.citation: Mol Biol Evol. 2008 Jun;25(6):1158-66
references.pmid: 18353797
references.citation: Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18064-8
references.pmid: 15596720
references.citation: Mol Microbiol. 1995 May;16(3):575-86
references.pmid: 7565116
references.citation: Proc Biol Sci. 2010 Jun 7;277(1688):1635-41
references.pmid: 20129981
references.citation: BMC Genomics. 2006 May 30;7:128
references.pmid: 16734888
references.citation: Mol Microbiol. 1998 Nov;30(3):647-56
references.pmid: 9822829
references.citation: BMC Microbiol. 2005 Oct 04;5:56
references.pmid: 16202144
references.citation: J Bacteriol. 2005 Feb;187(4):1276-86
references.pmid: 15687191
references.citation: Proc Natl Acad Sci U S A. 1982 Dec;79(24):7881-5
references.pmid: 6818556
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4447-52
references.pmid: 19251655
references.citation: Electrophoresis. 1998 Apr;19(4):593-6
references.pmid: 9588808
references.citation: J Exp Med. 1969 Jun 1;129(6):1327-48
references.pmid: 4977281
references.citation: Infect Immun. 1992 Nov;60(11):4704-8
references.pmid: 1398981
references.citation: Arch Oral Biol. 1971 Sep;16(9):1127-8
references.pmid: 5293413
references.citation: FEMS Microbiol Lett. 2009 Sep;298(1):20-8
references.pmid: 19659724
references.citation: Nature. 2009 Nov 5;462(7269):117-20
references.pmid: 19890332
references.citation: J Bacteriol. 1998 Feb;180(4):969-78
references.pmid: 9473054
references.citation: Anal Biochem. 1993 Mar;209(2):323-6
references.pmid: 8385891
references.citation: Mol Biol Evol. 2007 Aug;24(8):1596-9
references.pmid: 17488738
references.citation: Int J Pediatr Otorhinolaryngol. 2003 Oct;67(10):1047-53
references.pmid: 14550957
references.citation: Microbes Infect. 2000 May;2(6):687-700
references.pmid: 10884620
references.citation: Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3473-8
references.pmid: 18305155
references.citation: Mol Microbiol. 2000 Aug;37(4):839-55
references.pmid: 10972806
references.citation: Microbiology (Reading). 2006 Dec;152(Pt 12):3733-3749
references.pmid: 17159225
references.citation: J Mol Biol. 2002 Jan 25;315(4):859-71
references.pmid: 11812153
references.citation: Clin Microbiol Rev. 1989 Apr;2 Suppl:S1-4
references.pmid: 2470496
references.citation: FEMS Microbiol Lett. 1992 Jul 15;73(3):283-9
references.pmid: 1330818
references.citation: J Bacteriol. 2008 Aug;190(16):5576-86
references.pmid: 18556791
references.citation: J Bacteriol. 1987 Feb;169(2):790-5
references.pmid: 3100504
references.citation: Mol Biotechnol. 1996 Jun;5(3):233-41
references.pmid: 8837029
references.citation: Appl Microbiol. 1972 Nov;24(5):772-7
references.pmid: 4565636
references.citation: Mol Gen Genet. 1997 Nov;256(5):525-32
references.pmid: 9413436
references.citation: J Biol Chem. 1996 Apr 12;271(15):9114-9
references.pmid: 8621562
references.citation: J Clin Microbiol. 2000 Dec;38(12):4492-8
references.pmid: 11101585
references.citation: J Mol Evol. 1992 Feb;34(2):115-25
references.pmid: 1556747
references.citation: J Mol Biol. 2002 Feb 1;315(5):1111-27
references.pmid: 11827480
references.citation: Mol Microbiol. 2000 Jun;36(5):1049-58
references.pmid: 10844690
references.citation: J Bacteriol. 2010 May;192(9):2395-406
references.pmid: 20154126
references.citation: Methods Enzymol. 2008;437:539-60
references.pmid: 18433646