Impact of Sequence Non-Identities on Recombination within the pil System of Neisseria gonorrhoeae
ABSTRACT
Neisseria gonorrhoeae engages in extensive intra-cellular gene conversion between the PilE-expression locus (pilE) and the transcriptionally-silent pil gene copies (pilS). In silico analyses were applied to investigate the extent of sequence heterogeneity between the various pilS gene copies. Analysis of synonymous and non-synonymous substitutions between the different pilS genes indicated that relatively few amino acid changes would occur due to nucleotide polymorphisms towards the 5’ end of the pilS genes whereas more frequent amino acid substitutions would be incorporated within the “hypervariable” region. The lack of non-synonymous substitutions at the 5’ end of the genes was found to be under selective pressure as indicated by a positive DT score utilizing the Tajima test. The presence or absence of mismatch repair appeared to only impact recombination when non-identical DNAs recombined via the DNA transformation route, where small pil sequence heterogeneities were sufficient to terminate recombination tracts, with these sequence constraints being relieved in cells carrying a mutS mutation. Therefore, the data indicate that the effect of sequence heterogeneity on recombination within the pil system appears to depend upon the context with which the non-identical DNAs recombine.
Cite this paper
Hill, S. and Wachter, J. (2014) Impact of Sequence Non-Identities on Recombination within the pil System of Neisseria gonorrhoeae. Open Journal of Genetics, 4, 227-238. doi: 10.4236/ojgen.2014.43023.
Hill, S. and Wachter, J. (2014) Impact of Sequence Non-Identities on Recombination within the pil System of Neisseria gonorrhoeae. Open Journal of Genetics, 4, 227-238. doi: 10.4236/ojgen.2014.43023.
References
[1] Meyer, T.F. and Hill, S.A. (2003) Genetic Variation in the Pathogenic Neisseria spp. In: Craig, A. and Scherf, A., Eds., Antigenic Variation, Academic Press, Waltham, 142-164. [2] Swanson, J., Robbins, K., Barrera, O., Corwin, D., Boslego, J., Ciak, J., Blake, M. and Koomey, J.M. (1987) Gonococcal Pilin Variants in Experimental Gonorrhea. Journal of Experimental Medicine, 165, 1344-1357.
http://dx.doi.org/10.1084/jem.165.5.1344 [3] Meyer, T.F., Billyard, E., Haas, R., Storzbach, S. and So, M. (1984) Pilus Genes of Neisseria gonorrhoeae: Chromosomal Organization and DNA Sequence. Proceedings of the National Academy of Sciences of the United States of America, 81, 6110-6114.
http://dx.doi.org/10.1073/pnas.81.19.6110 [4] Haas, R. and Meyer, T.F. (1986) The Repertoire of Silent Pilus Genes in Neisseria gonorrhoeae: Evidence for Gene Conversion. Cell, 44, 107-115.
http://dx.doi.org/10.1016/0092-8674(86)90489-7 [5] Haas, R., Veit, S. and Meyer, T.F. (1992) Silent Pilin Genes of Neisseria gonorrhoeae MS11 and the Occurance of Related Hypervariant Sequences among other Gonococcal Isolates. Molecular Microbiology, 6, 197-208.
http://dx.doi.org/10.1111/j.1365-2958.1992.tb02001.x [6] Hagblom, P., Segal, E., Billyard, E. and So, M. (1985) Intragenic Recombination Leads to Pilus Antigenic Variation in Neisseria gonorrhoeae. Nature, 315, 156-158.
http://dx.doi.org/10.1038/315156a0 [7] Swanson, J., Morrison, S., Barrera, O. and Hill, S. (1990) Piliation Changes in Transformation-Defective Gonococci. Journal of Experimental Medicine, 171, 2131-2139.
http://dx.doi.org/10.1084/jem.171.6.2131 [8] Swanson, J., Berstrom, S., Robbins, K., Barrera, O., Corwin, D. and Koomey, J.M. (1986) Gene Conversion Involving the Pilin Structural Gene Correlates with Pilus+ to Pilus− Changes in Neisseria gonorrhoeae. Cell, 47, 267-276.
http://dx.doi.org/10.1016/0092-8674(86)90449-6 [9] Koomey, M., Gotschlich, E.C., Robbins, K., Bergstrom, S. and Swanson, J. (1987) Effects of recA Mutations on Pilus Antigenic Variation and Phase Transitions in Neisseria gonorrhoeae. Genetics, 117, 391-398. [10] Zhang, Q.Y., DeRyckere, D., Lauer, P. and Koomey, M. (1992) Gene Conversion in Neisseria gonorrhoeae: Evidence for Its Role in Pilus Antigenic Variation. Proceedings of the National Academy of Sciences of the United States of America, 89, 5366-5370.
http://dx.doi.org/10.1073/pnas.89.12.5366 [11] Cahoon, L.A. and Seifert, H.S. (2009) An Alternative DNA Structure Is Necessary for Pilin Antigenic Variation in Neisseria gonorrhoeae. Science, 32, 764-767.
http://dx.doi.org/10.1126/science.1175653 [12] Kowalczykowski, S.C., Dixon, D.A., Eggleston, A.K., Lauder, S.D. and Rehrauer, W.M. (1994) Biochemistry of Homologous Recombination in Escherichia coli. Microbiological Reviews, 58, 401-465. [13] Davidsen, T. and Tonjum, T. (2006) Meningococcal Genome Dynamics. Nature Reviews Microbiology, 4, 11-22.
http://dx.doi.org/10.1038/nrmicro1324 [14] Davidsen, T., Tuven, H.K., Bjoras, M., Rodland, E.A. and Tonjum, T. (2007) Genetic Interactions of DNA Repair Pathways in the Pathogen Neisseria meningitidis. Journal of Bacteriology, 189, 5728-5737.
http://dx.doi.org/10.1128/JB.00161-07 [15] Hill, S.A. and Davies, J.K. (2009) Pilin Gene Variation in Neisseria gonorrhoeae: Reassessing the Old Paradigms. FEMS Microbiological Reviews, 33, 521-531.
http://dx.doi.org/10.1111/j.1574-6976.2009.00171.x [16] Swanson, J. (1982) Colony Opacity and Protein II Compositions of Gonococci. Infection and Immunity, 37, 359-368. [17] Bergstrom, S., Robbins, K., Koomey, J.M. and Swanson, J. (1986) Piliation Control Mechanisms in Neisseria gonorrhoeae. Proceedings of the National Academy of Sciences of the United States of America, 83, 3890-3894.
http://dx.doi.org/10.1073/pnas.83.11.3890 [18] Hill, S.A., Morrison, S.G. and Swanson, J. (1992) The Role of Direct Oligonucleotide Repeats in Gonococcal Pilin Gene Variation. Molecular Microbiology, 4, 1341-1352.
http://dx.doi.org/10.1111/j.1365-2958.1990.tb00713.x [19] Hill, S.A., Woodward, T., Reger, A., Baker, R. and Dinse, T. (2007) Role for the RecBCD Recombination Pathway for pilE Gene Variation in Repair Proficient Neisseria gonorrhoeae. Journal of Bacteriology, 189, 7983-7990.
http://dx.doi.org/10.1128/JB.00980-07 [20] Wainwright, L.A., Pritchard, K.H. and Seifert, H.S. (1994) A Conserved DNA Sequence Is Required for Efficient Gonococcal Pilin Antigenic Variation. Molecular Microbiology, 13, 75-87.
http://dx.doi.org/10.1111/j.1365-2958.1994.tb00403.x [21] Seifert, H.S. (1997) Insertionally Inactivated and Inducible recA Alleles for Use in Neisseria. Gene, 188, 215-220.
http://dx.doi.org/10.1016/S0378-1119(96)00810-4 [22] Hill, S.A. (2000) Opa Expression Correlates with Elevated Transformation Rates in Neisseria gonorrhoeae. Journal of Bacteriology, 182, 171-178.
http://dx.doi.org/10.1128/JB.182.1.171-178.2000 [23] Gunn, J.S. and Stein, D.C. (1996) Use of a Non-Selective Transformation Technique to Construct a Multiply Restriction/Modification-Deficient Mutant of Neisseria gonorrhoeae. Molecular and General Genetics, 251, 509-517. [24] Katoh, S. (2013) MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability. Molecular Biology and Evolution, 30, 772-780.
http://dx.doi.org/10.1093/molbev/mst010 [25] Crooks, G.E, Hon, G., Chandonia, J.M. and Brenner, S.E. (2004) WebLogo: A Sequence Logo Generator. Genome Research, 14, 1188-1190.
http://dx.doi.org/10.1101/gr.849004 [26] Hartl, D.L., Moriyama, E.N. and Sawyer, S.A. (1994) Selection Intensity for Codon Bias. Genetics, 138, 227-234. [27] Librado, P.R.J. (2009) DnaSP v5: A Software for Comprehensive Analysis of DNA Polymorphism Data. Bioinformatics, 25, 1451-1452.
http://dx.doi.org/10.1093/bioinformatics/btp187 [28] Yang, Z. (2007) PAML 4: A Program Package for Phylogenetic Analysis by Maximum Likelihood. Molecular Biology and Evolution, 24, 1586-1591.
http://dx.doi.org/10.1093/molbev/msm088 [29] Criss, A.K., Bonney, K.M., Chang, R.A., Duffin, P.M., LeCuyer, B.E. and Seifert, H.S. (2010) Mismatch Correction Modulates Mutation Frequency and Pilus Phase and Antigenic Variation in Neisseria gonorrhoeae. Journal of Bacteriology, 192, 316-325.
http://dx.doi.org/10.1128/JB.01228-09 [30] Taddei, F., Radman, M., Maynard-Smith, J., Toupance, B., Gouyon, P.H. and Godelle, B. (1997) Role of Mutator Alleles in Adaptive Evolution. Nature, 387, 700-702.
http://dx.doi.org/10.1038/42696 [31] Richardson, A.R. and Stojiljkovic, I. (2001) Mismatch Repair and the Regulation of Phase Variation in Neisseria meningitidis. Molecular Microbiology, 40, 645-655.
http://dx.doi.org/10.1046/j.1365-2958.2001.02408.x [32] Richardson, A.R., Yu, Z., Popovic, T. and Stojiljkovic, I. (2002) Mutator Clones of neisseria meningitidis in Epidemic Serogroup A Disease. Proceedings of the National Academy of Sciences of the United States of America, 99, 6103-6107.
http://dx.doi.org/10.1073/pnas.092568699
[1] Meyer, T.F. and Hill, S.A. (2003) Genetic Variation in the Pathogenic Neisseria spp. In: Craig, A. and Scherf, A., Eds., Antigenic Variation, Academic Press, Waltham, 142-164. [2] Swanson, J., Robbins, K., Barrera, O., Corwin, D., Boslego, J., Ciak, J., Blake, M. and Koomey, J.M. (1987) Gonococcal Pilin Variants in Experimental Gonorrhea. Journal of Experimental Medicine, 165, 1344-1357.
http://dx.doi.org/10.1084/jem.165.5.1344 [3] Meyer, T.F., Billyard, E., Haas, R., Storzbach, S. and So, M. (1984) Pilus Genes of Neisseria gonorrhoeae: Chromosomal Organization and DNA Sequence. Proceedings of the National Academy of Sciences of the United States of America, 81, 6110-6114.
http://dx.doi.org/10.1073/pnas.81.19.6110 [4] Haas, R. and Meyer, T.F. (1986) The Repertoire of Silent Pilus Genes in Neisseria gonorrhoeae: Evidence for Gene Conversion. Cell, 44, 107-115.
http://dx.doi.org/10.1016/0092-8674(86)90489-7 [5] Haas, R., Veit, S. and Meyer, T.F. (1992) Silent Pilin Genes of Neisseria gonorrhoeae MS11 and the Occurance of Related Hypervariant Sequences among other Gonococcal Isolates. Molecular Microbiology, 6, 197-208.
http://dx.doi.org/10.1111/j.1365-2958.1992.tb02001.x [6] Hagblom, P., Segal, E., Billyard, E. and So, M. (1985) Intragenic Recombination Leads to Pilus Antigenic Variation in Neisseria gonorrhoeae. Nature, 315, 156-158.
http://dx.doi.org/10.1038/315156a0 [7] Swanson, J., Morrison, S., Barrera, O. and Hill, S. (1990) Piliation Changes in Transformation-Defective Gonococci. Journal of Experimental Medicine, 171, 2131-2139.
http://dx.doi.org/10.1084/jem.171.6.2131 [8] Swanson, J., Berstrom, S., Robbins, K., Barrera, O., Corwin, D. and Koomey, J.M. (1986) Gene Conversion Involving the Pilin Structural Gene Correlates with Pilus+ to Pilus− Changes in Neisseria gonorrhoeae. Cell, 47, 267-276.
http://dx.doi.org/10.1016/0092-8674(86)90449-6 [9] Koomey, M., Gotschlich, E.C., Robbins, K., Bergstrom, S. and Swanson, J. (1987) Effects of recA Mutations on Pilus Antigenic Variation and Phase Transitions in Neisseria gonorrhoeae. Genetics, 117, 391-398. [10] Zhang, Q.Y., DeRyckere, D., Lauer, P. and Koomey, M. (1992) Gene Conversion in Neisseria gonorrhoeae: Evidence for Its Role in Pilus Antigenic Variation. Proceedings of the National Academy of Sciences of the United States of America, 89, 5366-5370.
http://dx.doi.org/10.1073/pnas.89.12.5366 [11] Cahoon, L.A. and Seifert, H.S. (2009) An Alternative DNA Structure Is Necessary for Pilin Antigenic Variation in Neisseria gonorrhoeae. Science, 32, 764-767.
http://dx.doi.org/10.1126/science.1175653 [12] Kowalczykowski, S.C., Dixon, D.A., Eggleston, A.K., Lauder, S.D. and Rehrauer, W.M. (1994) Biochemistry of Homologous Recombination in Escherichia coli. Microbiological Reviews, 58, 401-465. [13] Davidsen, T. and Tonjum, T. (2006) Meningococcal Genome Dynamics. Nature Reviews Microbiology, 4, 11-22.
http://dx.doi.org/10.1038/nrmicro1324 [14] Davidsen, T., Tuven, H.K., Bjoras, M., Rodland, E.A. and Tonjum, T. (2007) Genetic Interactions of DNA Repair Pathways in the Pathogen Neisseria meningitidis. Journal of Bacteriology, 189, 5728-5737.
http://dx.doi.org/10.1128/JB.00161-07 [15] Hill, S.A. and Davies, J.K. (2009) Pilin Gene Variation in Neisseria gonorrhoeae: Reassessing the Old Paradigms. FEMS Microbiological Reviews, 33, 521-531.
http://dx.doi.org/10.1111/j.1574-6976.2009.00171.x [16] Swanson, J. (1982) Colony Opacity and Protein II Compositions of Gonococci. Infection and Immunity, 37, 359-368. [17] Bergstrom, S., Robbins, K., Koomey, J.M. and Swanson, J. (1986) Piliation Control Mechanisms in Neisseria gonorrhoeae. Proceedings of the National Academy of Sciences of the United States of America, 83, 3890-3894.
http://dx.doi.org/10.1073/pnas.83.11.3890 [18] Hill, S.A., Morrison, S.G. and Swanson, J. (1992) The Role of Direct Oligonucleotide Repeats in Gonococcal Pilin Gene Variation. Molecular Microbiology, 4, 1341-1352.
http://dx.doi.org/10.1111/j.1365-2958.1990.tb00713.x [19] Hill, S.A., Woodward, T., Reger, A., Baker, R. and Dinse, T. (2007) Role for the RecBCD Recombination Pathway for pilE Gene Variation in Repair Proficient Neisseria gonorrhoeae. Journal of Bacteriology, 189, 7983-7990.
http://dx.doi.org/10.1128/JB.00980-07 [20] Wainwright, L.A., Pritchard, K.H. and Seifert, H.S. (1994) A Conserved DNA Sequence Is Required for Efficient Gonococcal Pilin Antigenic Variation. Molecular Microbiology, 13, 75-87.
http://dx.doi.org/10.1111/j.1365-2958.1994.tb00403.x [21] Seifert, H.S. (1997) Insertionally Inactivated and Inducible recA Alleles for Use in Neisseria. Gene, 188, 215-220.
http://dx.doi.org/10.1016/S0378-1119(96)00810-4 [22] Hill, S.A. (2000) Opa Expression Correlates with Elevated Transformation Rates in Neisseria gonorrhoeae. Journal of Bacteriology, 182, 171-178.
http://dx.doi.org/10.1128/JB.182.1.171-178.2000 [23] Gunn, J.S. and Stein, D.C. (1996) Use of a Non-Selective Transformation Technique to Construct a Multiply Restriction/Modification-Deficient Mutant of Neisseria gonorrhoeae. Molecular and General Genetics, 251, 509-517. [24] Katoh, S. (2013) MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability. Molecular Biology and Evolution, 30, 772-780.
http://dx.doi.org/10.1093/molbev/mst010 [25] Crooks, G.E, Hon, G., Chandonia, J.M. and Brenner, S.E. (2004) WebLogo: A Sequence Logo Generator. Genome Research, 14, 1188-1190.
http://dx.doi.org/10.1101/gr.849004 [26] Hartl, D.L., Moriyama, E.N. and Sawyer, S.A. (1994) Selection Intensity for Codon Bias. Genetics, 138, 227-234. [27] Librado, P.R.J. (2009) DnaSP v5: A Software for Comprehensive Analysis of DNA Polymorphism Data. Bioinformatics, 25, 1451-1452.
http://dx.doi.org/10.1093/bioinformatics/btp187 [28] Yang, Z. (2007) PAML 4: A Program Package for Phylogenetic Analysis by Maximum Likelihood. Molecular Biology and Evolution, 24, 1586-1591.
http://dx.doi.org/10.1093/molbev/msm088 [29] Criss, A.K., Bonney, K.M., Chang, R.A., Duffin, P.M., LeCuyer, B.E. and Seifert, H.S. (2010) Mismatch Correction Modulates Mutation Frequency and Pilus Phase and Antigenic Variation in Neisseria gonorrhoeae. Journal of Bacteriology, 192, 316-325.
http://dx.doi.org/10.1128/JB.01228-09 [30] Taddei, F., Radman, M., Maynard-Smith, J., Toupance, B., Gouyon, P.H. and Godelle, B. (1997) Role of Mutator Alleles in Adaptive Evolution. Nature, 387, 700-702.
http://dx.doi.org/10.1038/42696 [31] Richardson, A.R. and Stojiljkovic, I. (2001) Mismatch Repair and the Regulation of Phase Variation in Neisseria meningitidis. Molecular Microbiology, 40, 645-655.
http://dx.doi.org/10.1046/j.1365-2958.2001.02408.x [32] Richardson, A.R., Yu, Z., Popovic, T. and Stojiljkovic, I. (2002) Mutator Clones of neisseria meningitidis in Epidemic Serogroup A Disease. Proceedings of the National Academy of Sciences of the United States of America, 99, 6103-6107.
http://dx.doi.org/10.1073/pnas.092568699