1887

Abstract

There are many types of repeated DNA sequences in the genomes of the species of the genus Neisseria, from homopolymeric tracts to tandem repeats of hundreds of bases. Some of these have roles in the phase-variable expression of genes. When a repeat mediates phase variation, reversible switching between tract lengths occurs, which in the species of the genus Neisseria most often causes the gene to switch between on and off states through frame shifting of the open reading frame. Changes in repeat tract lengths may also influence the strength of transcription from a promoter. For phenotypes that can be readily observed, such as expression of the surface-expressed Opa proteins or pili, verification that repeats are mediating phase variation is relatively straightforward. For other genes, particularly those where the function has not been identified, gathering evidence of repeat tract changes can be more difficult. Here we present analysis of the repetitive sequences that could mediate phase variation in the Neisseria gonorrhoeae strain NCCP11945 genome sequence and compare these results with other gonococcal genome sequences. Evidence is presented for an updated phase-variable gene repertoire in this species, including a class of phase variation that causes amino acid changes at the C-terminus of the protein, not previously described in N. gonorrhoeae.

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2016-08-25
2019-10-13
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References

  1. Adamczyk-Poplawska M., Lower M., Piekarowicz A.. 2011; Deletion of one nucleotide within the homonucleotide tract present in the hsdS gene alters the DNA sequence specificity of type I restriction-modification system NgoAV. J Bacteriol193:6750–6759 [CrossRef][PubMed]
    [Google Scholar]
  2. Afgan E., Baker D., Van den Beek M., Blankenberg D., Bouvier D., Čech M., Chilton J., Clements D., Coraor N. et al. 2016; The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2016 update. Nucleic Acids Res44:W3–W10 [CrossRef][PubMed]
    [Google Scholar]
  3. Arenas J., Cano S., Nijland R., Van Dongen V., Rutten L., Van der Ende A., Tommassen J.. 2015; The meningococcal autotransporter AutA is implicated in autoaggregation and biofilm formation. Environ Microbiol17:1321–1337 [CrossRef][PubMed]
    [Google Scholar]
  4. Banerjee A., Wang R., Supernavage S. L., Ghosh S. K., Parker J., Ganesh N. F., Wang P. G., Gulati S., Rice P. A.. 2002; Implications of phase variation of a gene (pgtA) encoding a pilin galactosyl transferase in gonococcal pathogenesis. J Exp Med196:147–162 [CrossRef][PubMed]
    [Google Scholar]
  5. Barnett D. W., Garrison E. K., Quinlan A. R., Strömberg M. P., Marth G. T.. 2011; BamTools: a C++ API and toolkit for analyzing and managing BAM files. Bioinformatics27:1691–1692 [CrossRef][PubMed]
    [Google Scholar]
  6. Bhat K. S., Gibbs C. P., Barrera O., Morrison S. G., Jähnig F., Stern A., Kupsch E. M., Meyer T. F., Swanson J.. 1991; The opacity proteins of Neisseria gonorrhoeae strain MS11 are encoded by a family of 11 complete genes. Mol Microbiol5:1889–1901 [CrossRef][PubMed]
    [Google Scholar]
  7. Blankenberg D., Gordon A., Von Kuster G., Coraor N., Taylor J., Nekrutenko A.. Galaxy Team 2010; Manipulation of FASTQ data with Galaxy. Bioinformatics26:1783–1785 [CrossRef][PubMed]
    [Google Scholar]
  8. Bolotin D. A., Mamedov I. Z., Britanova O. V., Zvyagin I. V., Shagin D., Ustyugova S. V., Turchaninova M. A., Lukyanov S., Lebedev Y. B., Chudakov D. M.. 2012; Next generation sequencing for TCR repertoire profiling: platform-specific features and correction algorithms. Eur J Immunol42:3073–3083 [CrossRef][PubMed]
    [Google Scholar]
  9. Bragg L. M., Stone G., Butler M. K., Hugenholtz P., Tyson G. W.. 2013; Shining a light on dark sequencing: characterising errors in Ion torrent PGM data. PLoS Comput Biol9:e1003031 [CrossRef][PubMed]
    [Google Scholar]
  10. Carbonnelle E., Hill D. J., Morand P., Griffiths N. J., Bourdoulous S., Murillo I., Nassif X., Virji M.. 2009; Meningococcal interactions with the host. Vaccine27:B78–89 [CrossRef][PubMed]
    [Google Scholar]
  11. Carson S. D., Stone B., Beucher M., Fu J., Sparling P. F.. 2000; Phase variation of the gonococcal siderophore receptor FetA. Mol Microbiol36:585–593 [CrossRef][PubMed]
    [Google Scholar]
  12. Chaudhuri R. R., Loman N. J., Snyder L. A., Bailey C. M., Stekel D. J., Pallen M. J.. 2008; xBASE2: a comprehensive resource for comparative bacterial genomics. Nucleic Acids Res36:D543–546 [CrossRef][PubMed]
    [Google Scholar]
  13. Chen C. J., Elkins C., Sparling P. F.. 1998; Phase variation of hemoglobin utilization in Neisseria gonorrhoeae. Infect Immun66:987–993[PubMed]
    [Google Scholar]
  14. Chung G. T., Yoo J. S., Oh H. B., Lee Y. S., Cha S. H., Kim S. J., Yoo C. K.. 2008; Complete genome sequence of Neisseria gonorrhoeae NCCP11945. J Bacteriol190:6035–6036 [CrossRef][PubMed]
    [Google Scholar]
  15. Darling A. C., Mau B., Blattner F. R., Perna N. T.. 2004; Mauve: multiple alignment of conserved genomic sequence with rearrangements. Genome Res14:1394–1403 [CrossRef][PubMed]
    [Google Scholar]
  16. Erwin A. L., Haynes P. A., Rice P. A., Gotschlich E. C.. 1996; Conservation of the lipooligosaccharide synthesis locus lgt among strains of Neisseria gonorrhoeae: requirement for lgtE in synthesis of the 2C7 epitope and of the β chain of strain 15253. J Exp Med184:1233–1241 [CrossRef][PubMed]
    [Google Scholar]
  17. Jamet A., Jousset A. B., Euphrasie D., Mukorako P., Boucharlat A., Ducousso A., Charbit A., Nassif X.. 2015; A new family of secreted toxins in pathogenic Neisseria species. PLoS Pathog11:e1004592 [CrossRef][PubMed]
    [Google Scholar]
  18. Janulczyk R., Masignani V., Maione D., Tettelin H., Grandi G., Telford J. L.. 2010; Simple sequence repeats and genome plasticity in Streptococcus agalactiae. J Bacteriol192:3990–4000 [CrossRef][PubMed]
    [Google Scholar]
  19. Jonsson A. B., Nyberg G., Normark S.. 1991; Phase variation of gonococcal pili by frameshift mutation in pilC, a novel gene for pilus assembly. EMBO J10:477–488[PubMed]
    [Google Scholar]
  20. Jordan P. W., Snyder L. A., Saunders N. J.. 2005; Strain-specific differences in Neisseria gonorrhoeae associated with the phase variable gene repertoire. BMC Microbiol5: [CrossRef][PubMed]
    [Google Scholar]
  21. Kellogg D. S. Jr, Peacock W. L. Jr, Deacon W. E., Brown L., Pirkle D. I.. 1963; Neisseria gonorrhoeae I. virulence genetically linked to clonal variation. J Bacteriol85:1274–1279
    [Google Scholar]
  22. Langmead B., Trapnell C., Pop M., Salzberg S. L.. 2009; Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol10:R25 [CrossRef][PubMed]
    [Google Scholar]
  23. Langmead B., Salzberg S. L.. 2012; Fast gapped-read alignment with Bowtie 2. Nat Methods9:357–359 [CrossRef][PubMed]
    [Google Scholar]
  24. Lewis L. A., Gipson M., Hartman K., Ownbey T., Vaughn J., Dyer D. W.. 1999; Phase variation of HpuAB and HmbR, two distinct haemoglobin receptors of Neisseria meningitidis DNM2. Mol Microbiol32:977–989 [CrossRef][PubMed]
    [Google Scholar]
  25. Loman N. J., Misra R. V., Dallman T. J., Constantinidou C., Gharbia S. E., Wain J., Pallen M. J.. 2012; Performance comparison of benchtop high-throughput sequencing platforms. Nat Biotechnol30:434–439 [CrossRef][PubMed]
    [Google Scholar]
  26. Mackinnon F. G., Cox A. D., Plested J. S., Tang C. M., Makepeace K., Coull P. A., Wright J. C., Chalmers R., Hood D. W. et al. 2002; Identification of a gene (lpt-3) required for the addition of phosphoethanolamine to the lipopolysaccharide inner core of Neisseria meningitidis and its role in mediating susceptibility to bactericidal killing and opsonophagocytosis. Mol Microbiol43:931–943 [CrossRef][PubMed]
    [Google Scholar]
  27. Martin P., Van de Ven T., Mouchel N., Jeffries A. C., Hood D. W., Moxon E. R.. 2003; Experimentally revised repertoire of putative contingency loci in Neisseria meningitidis strain MC58: evidence for a novel mechanism of phase variation. Mol Microbiol50:245–257 [CrossRef][PubMed]
    [Google Scholar]
  28. Moxon R., Bayliss C., Hood D.. 2006; Bacterial contingency loci: the role of simple sequence DNA repeats in bacterial adaptation. Annu Rev Genet40:307–333 [CrossRef][PubMed]
    [Google Scholar]
  29. Muralidharan K., Stern A., Meyer T. F.. 1987; The control mechanism of opacity protein expression in the pathogenic Neisseriae. Antonie Van Leeuwenhoek53:435–440 [CrossRef][PubMed]
    [Google Scholar]
  30. Narzisi G., Schatz M. C.. 2015; The challenge of small-scale repeats for indel discovery. Front Bioeng Biotechnol3:8 [CrossRef][PubMed]
    [Google Scholar]
  31. Omer H., Rose G., Jolley K. A., Frapy E., Zahar J. R., Maiden M. C., Bentley S. D., Tinsley C. R., Nassif X., Bille E.. 2011; Genotypic and phenotypic modifications of Neisseria meningitidis after an accidental human passage. PLoS One6:e17145 [CrossRef][PubMed]
    [Google Scholar]
  32. Peak I. R., Jennings M. P., Hood D. W., Moxon E. R.. 1999; Tetranucleotide repeats identify novel virulence determinant homologues in Neisseria meningitidis. Microb Pathog26:13–23 [CrossRef][PubMed]
    [Google Scholar]
  33. Power P. M., Roddam L. F., Rutter K., Fitzpatrick S. Z., Srikhanta Y. N., Jennings M. P.. 2003; Genetic characterization of pilin glycosylation and phase variation in Neisseria meningitidis. Mol Microbiol49:833–847 [CrossRef][PubMed]
    [Google Scholar]
  34. Quail M. A., Smith M., Coupland P., Otto T. D., Harris S. R., Connor T. R., Bertoni A., Swerdlow H. P., Gu Y.. 2012; A tale of three next generation sequencing platforms: comparison of Ion Torrent, Pacific Biosciences and Illumina MiSeq sequencers. BMC Genomics13:341 [CrossRef][PubMed]
    [Google Scholar]
  35. Robinson J. T., Thorvaldsdóttir H., Winckler W., Guttman M., Lander E. S., Getz G., Mesirov J. P.. 2011; Integrative genomics viewer. Nat Biotechnol29:24–26 [CrossRef][PubMed]
    [Google Scholar]
  36. Schirmer M., Ijaz U. Z., D'Amore R., Hall N., Sloan W. T., Quince C.. 2015; Insight into biases and sequencing errors for amplicon sequencing with the Illumina MiSeq platform. Nucleic Acids Res43:e37 [CrossRef][PubMed]
    [Google Scholar]
  37. Shafer W. M., Datta A., Kolli V. S., Rahman M. M., Balthazar J. T., Martin L. E., Veal W. L., Stephens D. S., Carlson R.. 2002; Phase variable changes in genes lgtA and lgtC within the lgtABCDE operon of Neisseria gonorrhoeae can modulate gonococcal susceptibility to normal human serum. J Endotoxin Res8:47–58 [CrossRef][PubMed]
    [Google Scholar]
  38. Snyder L. A., Butcher S. A., Saunders N. J.. 2001; Comparative whole-genome analyses reveal over 100 putative phase-variable genes in the pathogenic Neisseria spp. Microbiology147:2321–2332 [CrossRef][PubMed]
    [Google Scholar]
  39. Snyder L. A., Loman N. J., Linton J. D., Langdon R. R., Weinstock G. M., Wren B. W., Pallen M. J.. 2010; Simple sequence repeats in Helicobacter canadensis and their role in phase variable expression and C-terminal sequence switching. BMC Genomics11: [CrossRef][PubMed]
    [Google Scholar]
  40. Sparling P. F., Cannon J. G., So M.. 1986; Phase and antigenic variation of pili and outer membrane protein II of Neisseria gonorrhoeae. J Infect Dis153:196–201 [CrossRef][PubMed]
    [Google Scholar]
  41. Srikhanta Y. N., Dowideit S. J., Edwards J. L., Falsetta M. L., Wu H. J., Harrison O. B., Fox K. L., Seib K. L., Maguire T. L. et al. 2009; Phasevarions mediate random switching of gene expression in pathogenic Neisseria. PLoS Pathog5:e1000400 [CrossRef][PubMed]
    [Google Scholar]
  42. Stern A., Meyer T. F.. 1987; Common mechanism controlling phase and antigenic variation in pathogenic neisseriae. Mol Microbiol1:5–12 [CrossRef][PubMed]
    [Google Scholar]
  43. Thorvaldsdóttir H., Robinson J. T., Mesirov J. P.. 2013; Integrative genomics viewer (IGV): high-performance genomics data visualization and exploration. Brief Bioinform14:178–192 [CrossRef][PubMed]
    [Google Scholar]
  44. Van der Ende A., Hopman C. T., Zaat S., Essink B. B., Berkhout B., Dankert J.. 1995; Variable expression of class 1 outer membrane protein in Neisseria meningitidis is caused by variation in the spacing between the −10 and −35 regions of the promoter. J Bacteriol177:2475–2480[PubMed]
    [Google Scholar]
  45. Viburiene R., Vik Å., Koomey M., Børud B.. 2013; Allelic variation in a simple sequence repeat element of neisserial pglB2 and its consequences for protein expression and protein glycosylation. J Bacteriol195:3476–3485 [CrossRef][PubMed]
    [Google Scholar]
  46. Yang Q. L., Gotschlich E. C.. 1996; Variation of gonococcal lipooligosaccharide structure is due to alterations in poly-G tracts in lgt genes encoding glycosyl transferases. J Exp Med183:323–327 [CrossRef][PubMed]
    [Google Scholar]
  47. Zelewska, M. A., Pulijala, M., & Snyder, L. A. S., NCBI Sequence Read Archive. Accession number SRR3547950 2016
  48. Mahmood, H. -T. -N. A., & Snyder, L. A. S., NCBI Sequence Read Archive. Accession number SRR3547951 2016
  49. Churchward, C. P., Calder, A., & Snyder, L. A. S., NCBI Sequence Read Archive. Accession number SRR3547952 2016
  50. Churchward, C. P., Calder, A., & Snyder, L. A. S., NCBI Sequence Read Archive. Accession number SRR3547953 2016
  51. Churchward, C. P., Calder, A., & Snyder, L. A. S., NCBI Sequence Read Archive. Accession number SRR3547954 2016
  52. Churchward, C. P., Calder, A., & Snyder, L. A. S., NCBI Sequence Read Archive. Accession number SRR3547955 2016
  53. Churchward, C. P., Calder, A., & Snyder, L. A. S., NCBI Sequence Read Archive. Accession number SRR3547956 2016
  54. Churchward, C. P., Calder, A., & Snyder, L. A. S., NCBI Sequence Read Archive. Accession number SRR3547957 2016
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