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2 - Bacterial Recombination in vivo

from PART I - Theoretical Considerations on the Evolution of Bacterial Pathogens

Published online by Cambridge University Press:  16 September 2009

By
Xavier Didelot  and
Daniel Falush
Edited by
Michael Hensel  and
Herbert Schmidt
Michael Hensel
Affiliation:
Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany
Herbert Schmidt
Affiliation:
Universität Hohenheim, Stuttgart
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Summary

INTRODUCTION

In eukaryotes, the great majority of genetic recombination takes place during the complex and highly organized process of meiotic division, a part of sexual reproduction. As a consequence there are a number of constraints on patterns of variability in the recombination process. Recombination takes place only between organisms that are similar enough for their offspring to be viable, and therefore it is generally limited in the novelty it can introduce. Within species, the most common cause of reproductive isolation is geographical separation. In most higher animals and plants, the number of crossovers per chromosome is predictably a number between 1 and 5 in both sexes. Even where individuals differ in the amount of recombination that they initiate, for example because of the absence of crossing over in male Drosophila, the existence of a common mating pool will tend to homogenize the population with respect to the amount of genetic exchange that has occurred in the ancestry of each individual. In summary, while the mating process is elegant, eukaryotic recombination is typically quite predictable with minimal differences in genetic patterns between individuals in the same species.

In bacteria, there are no such rules. Recombination is never obligate and occurs by three distinct mechanisms; transformation, transduction, and conjugation, each of which in their nature can vary enormously between lineages.

Type
Chapter
Information
Horizontal Gene Transfer in the Evolution of Pathogenesis , pp. 23 - 46
Publisher: Cambridge University Press
Print publication year: 2008

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References

Achtman, M. (2004). Population structure of pathogenic bacteria revisited. Int J Med Microbiol, 294, 67–73.CrossRefGoogle ScholarPubMed
Achtman, M., Zurth, K., Morelli, G., et al. (1999). Yersinia pestis, the cause of plague, is a recently emerged clone of Yersinia pseudotuberculosis. Proc Natl Acad Sci USA, 96, 14043–48.CrossRefGoogle ScholarPubMed
Achtman, M., Morelli, G., Zhu, P.et al. (2004). Microevolution and history of the plague bacillus, Yersinia pestis. Proc Natl Acad Sci USA, 101, 17837–42.CrossRefGoogle ScholarPubMed
Anderson, E. S., and R. E, Williams. (1956). Bacteriophage typing of enteric pathogens and staphylococci and its use in epidemiology. J Clin Pathol, 9, 94–127.CrossRefGoogle ScholarPubMed
Baldo, L., J., Hotopp, C. D., Jolley, K. A., et al. (2006). A multilocus sequence typing system for the endosymbiont Wolbachia. Appl Environ Microbiol, 72, 7098–110.CrossRefGoogle ScholarPubMed
Bisharat, N., Cohen, D. I., Harding, R. M., et al. (2005). Hybrid Vibrio vulnificus. Emerg Infect Dis, 11, 30–5.CrossRefGoogle ScholarPubMed
Bjorkholm, B., Sjolund, M., Falk, P. G., et al. (2001). Mutation frequency and biological cost of antibiotic resistance in Helicobacter pylori. Proc Natl Acad Sci USA, 98, 14607–12.CrossRefGoogle ScholarPubMed
Brown, A., Feldman, M., and Nevo, E. (1980). Multilocus structure of natural populations of Hordeum spontaneum. Genetics, 96, 523–36.Google ScholarPubMed
Buchanan-Wollaston, V., Passiatore, J. E., and Cannon, F. (1987). The mob and oriT mobilization functions of a bacterial plasmid promote its transfer to plants. Nature, 328, 172–5.CrossRefGoogle Scholar
Cheetham, B. F., and Katz, M. E. (1995). A role for bacteriophages in the evolution and transfer of bacterial virulence determinants. Mol Microbiol, 18, 201–8.CrossRefGoogle ScholarPubMed
Chibani-Chennoufi, S., Bruttin, A., Dillmann, M. L., and Br, H. (2004). Phage-host interaction: an ecological perspective. J Bacteriol, 186, 3677–86.CrossRefGoogle Scholar
Clewell, D. B., Flannagan, S. E., and Jaworski, D. D. (1995). Unconstrained bacterial promiscuity: the Tn916-Tn1545 family of conjugative transposons. Trends Microbiol, 3, 229–36.CrossRefGoogle ScholarPubMed
Daubin, V., Lerat, E., and Perriere, G. (2003). The source of laterally transferred genes in bacterial genomes. Genome Biol, 4, R57.CrossRefGoogle ScholarPubMed
Davison, J. (1999). Genetic exchange between bacteria in the environment. Plasmid, 42, 73–91.CrossRefGoogle ScholarPubMed
Denamur, E., and Matic, I. (2006). Evolution of mutation rates in bacteria. Mol Microbiol, 60, 820–7.CrossRefGoogle ScholarPubMed
Didelot, X., and Falush, D. (2007). Inference of bacterial microevolution using multilocus sequence data. Genetics, 175, 1251–66.CrossRefGoogle ScholarPubMed
Didelot, X., Achtman, M., Parkhill, J., Thomson, N. R., and Falush, D. (2007). A bimodal pattern of relatedness between the Salmonella Paratyphi A and Typhi genomes: convergence or divergence by homologous recombination?Genome Res, 17, 61–8.CrossRefGoogle ScholarPubMed
Dingle, K. E., Colles, F. M., Falush, D., and Maiden, M. C. (2005). Sequence typing and comparison of population biology of Campylobacter coli and Campylobacter jejuni. J Clin Microbiol, 43, 340–7.CrossRefGoogle ScholarPubMed
Dubnau, D. (1999). DNA uptake in bacteria. Annu Rev Microbiol, 53, 217–44.CrossRefGoogle ScholarPubMed
Falush, D., Kraft, C., Taylor, N. S., et al. (2001). Recombination and mutation during long-term gastric colonization by Helicobacter pylori: estimates of clock rates, recombination size, and minimal age. Proc Natl Acad Sci USA, 98, 15056–61.CrossRefGoogle ScholarPubMed
Falush, D., Stephens, M., and Pritchard, J. K. (2003a). Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies. Genetics, 164, 1567–87.Google ScholarPubMed
Falush, D., Wirth, T., Linz, B., et al. (2003b). Traces of human migrations in Helicobacter pylori populations. Science, 299, 1582–5.CrossRefGoogle ScholarPubMed
Falush, D., Torpdahl, M., Didelot, X., et al. (2006). Mismatch induced speciation in Salmonella: model and data. Phil Trans R Soc B, 361, 2045–53.CrossRefGoogle ScholarPubMed
Fearnhead, P., and Donnelly, P. (2001). Estimating recombination rates from population genetic data. Genetics, 159, 1299–318.Google ScholarPubMed
Fearnhead, P., Smith, N. G., Barrigas, M., Fox, A., and French, N. (2005). Analysis of recombination in Campylobacter jejuni from MLST population data. J Mol Evol, 61, 333–40.CrossRefGoogle ScholarPubMed
Feil, E., Zhou, J., Smith, J Maynard., and Spratt, B. G. (1996). A comparison of the nucleotide sequences of the adk and recA genes of pathogenic and commensal Neisseria species: evidence for extensive interspecies recombination within adk. J Mol Evol, 43, 631–40.CrossRefGoogle ScholarPubMed
Feil, E., Maiden, M., Achtman, M., and Spratt, B. (1999). The relative contributions of recombination and mutation to the divergence of clones of Neisseria meningitidis. Mol Biol Evol, 16, 1496–502.CrossRefGoogle ScholarPubMed
Feil, E. J., Smith, J. M., Enright, M. C., and Spratt, B. G. (2000). Estimating recombinational parameters in Streptococcus pneumoniae from Multilocus Sequence Typing data. Genetics, 154, 1439–50.Google ScholarPubMed
Feil, E. J., Holmes, E. C., Enright, M. C., et al. (2001). Recombination within natural populations of pathogenic bacteria: short-term empirical estimates and long-term phylogenetic consequences. Proc Natl Acad Sci USA, 98, 182–7.CrossRefGoogle ScholarPubMed
Feil, E. J., Cooper, J. E., Grundmann, H., et al. (2003). How clonal is Staphylococcus aureus?J Bacteriol, 185, 3307–16.CrossRefGoogle ScholarPubMed
Feil, E. J., Li, B. C., Aanensen, D. M., Hanage, W. P., and Spratt, B. G. (2004). eBURST: Inferring patterns of evolutionary descent among clusters of related bacterial genotypes from Multilocus Sequence Typing data. J Bacteriol, 186, 1518–30.CrossRefGoogle ScholarPubMed
Fraser, C., Hanage, W. P., and Spratt, B. G. (2005). Neutral microepidemic evolution of bacterial pathogens. Proc Natl Acad Sci USA, 102, 1968–73.CrossRefGoogle ScholarPubMed
Giraud, A., Matic, I., Tenaillon, O., et al. (2001). Costs and benefits of high mutation rates: adaptive evolution of bacteria in the mouse gut. Science, 291, 2606–8.CrossRefGoogle ScholarPubMed
Goodman, S. D., and Scocca, J. J. (1988). Identification and arrangement of the DNA sequence recognized in specific transformation of Neisseria gonorrhoeae. Proc Natl Acad Sci USA, 85, 6982–6.CrossRefGoogle ScholarPubMed
Goss, E. M., Kreitman, M., and Bergelson, J. (2005). Genetic diversity, recombination and cryptic clades in Pseudomonas viridiava infecting natural populations of Arabidopsis thaliana. Genetics, 169, 21–35.CrossRefGoogle ScholarPubMed
Griffiths, R., and Marjoram, P. (1996). Ancestral inference from samples of DNA sequences with recombination. J Comput Biol, 3, 479–502.CrossRefGoogle ScholarPubMed
Groisman, E. A., and Ochman, H. (1997). How Salmonella became a pathogen. Trends Microbiol, 5, 343–9.CrossRefGoogle ScholarPubMed
Gutierrez, M. C., Brisse, S., Brosch, R.et al. (2005). Ancient origin and gene mosaicism of the progenitor of Mycobacterium tuberculosis. PLoS Pathog, 1, e5.CrossRefGoogle ScholarPubMed
Guttman, D. S., and Dykhuizen, D. E. (1994). Clonal divergence in Escherichia coli as a result of recombination, not mutation. Science, 266, 1380–3.CrossRefGoogle Scholar
Hacker, J., Blum-Oehler, G., Muhldorfer, I., and Tschäpe, H. (1997). Pathogenicity islands of virulent bacteria: structure, function and impact on microbial evolution. Mol Microbiol, 23, 1089–97.CrossRefGoogle ScholarPubMed
Hall, R. M., and Collis, C. M. (1995). Mobile gene cassettes and integrons: capture and spread of genes by site-specific recombination. Mol Microbiol, 15, 593–600.CrossRefGoogle ScholarPubMed
Hanage, W. P., Fraser, C., and Spratt, B. G. (2005). Fuzzy species among recombinogenic bacteria. BMC Biol, 3, 6–6.CrossRefGoogle ScholarPubMed
Hanage, W. P., Spratt, B. G., Turner, K. M. E., and Fraser, C. (2006). Modelling bacterial speciation. Phil Trans R Soc B, 361, 2039–44.CrossRefGoogle ScholarPubMed
Heinemann, J. A., and Sprague, G. F. (1989). Bacterial conjugative plasmids mobilize DNA transfer between bacteria and yeast. Nature, 340, 205–9.CrossRefGoogle ScholarPubMed
Hiramatsu, K., Watanabe, S., Takeuchi, F., Ito, T., and Baba, T. (2004). Genetic characterization of methicillin-resistant Staphylococcus aureus. Vaccine, 22 Suppl 1, 5–8.CrossRefGoogle ScholarPubMed
Homan, W. L., Tribe, D., Poznanski, S., et al. (2002). Multilocus sequence typing scheme for Enterococcus faecium. J Clin Microbiol, 40, 1963–71.CrossRefGoogle ScholarPubMed
Hudson, R. R. (1983). Properties of a neutral allele model with intragenic recombination. Theor Popul Biol, 23, 183–201.CrossRefGoogle ScholarPubMed
Hudson, R. R. (2001). Two-locus sampling distributions and their application. Genetics, 159, 1805–17.Google ScholarPubMed
Jolley, K. A., Kalmusova, J., Feil, E. J., et al. (2000). Carried meningococci in the Czech Republic: a diverse recombining population. J Clin Microbiol, 38, 4492–8.Google ScholarPubMed
Jolley, K. A., Wilson, D. J., Kriz, P., McVean, G., and Maiden, M. C. J. (2005). The inluence of mutation, recombination, population history, and selection on patterns of genetic diversity in Neisseria meningitidis. Mol Biol Evol, 22, 562–9.CrossRefGoogle Scholar
King, S. J., Whatmore, A. M., and Dowson, C. G. (2005). NanA, a neuraminidase from Streptococcus pneumoniae, shows high levels of sequence diversity, at least in part through recombination with Streptococcus oralis. J Bacteriol, 187, 5376–86.CrossRefGoogle ScholarPubMed
Kotetishvili, M., Kreger, A., Wauters, G., et al. (2005). Multilocus sequence typing for studying genetic relationships among Yersinia species. J Clin Microbiol, 43, 2674–84.CrossRefGoogle ScholarPubMed
Kremer, K., Soolingen, D., Frothingham, R., et al. (1999). Comparison of methods based on different molecular epidemiological markers for typing of Mycobacterium tuberculosis complex strains: interlaboratory study of discriminatory power and reproducibility. J Clin Microbiol, 37, 2607–18.Google ScholarPubMed
Kuhner, M. K., Yamato, J., and Felsenstein, J. (2000). Maximum likelihood estimation of recombination rates from population data. Genetics, 156, 1393–401.Google ScholarPubMed
Minor, L. (1988). Typing of Salmonella species. Eur J Clin Microbiol Infect Dis, 7, 214–8.CrossRefGoogle ScholarPubMed
Linz, B., Schenker, M., Zhu, P., and Achtman, M. (2000). Frequent interspecific genetic exchange between commensal Neisseriae and Neisseria meningitidis. Mol Microbiol, 36, 1049–58.CrossRefGoogle ScholarPubMed
Lorenz, M. G., and Wackernagel, W. (1994). Bacterial gene transfer by natural genetic transformation in the environment. Microbiol Rev, 58, 563–602.Google ScholarPubMed
Maiden, M. C., Bygraves, J. A., Feil, E., et al. (1998). Multi-locus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc Natl Acad Sci USA, 95, 3140–5.CrossRefGoogle Scholar
Majewski, J., and Cohan, F. M. (1998). The effect of mismatch repair and heteroduplex formation on sexual isolation in Bacillus. Genetics, 148, 13–8.Google ScholarPubMed
Majewski, J., and Cohan, F. M. (1999). DNA sequence similarity requirements for interspecific recombination in Bacillus. Genetics, 153, 1525–33.Google ScholarPubMed
Majewski, J., Zawadzki, P., Pickerill, P., Cohan, F. M., and Dowson, C. G. (2000). Barriers to genetic exchange between bacterial species: Streptococcus pneumoniae transformation. J Bacteriol, 182, 1016–23.CrossRefGoogle ScholarPubMed
Maynard Smith, J., Smith, N., O'Rourke, M., and Spratt, B. (1993). How clonal are bacteria?Proc Natl Acad Sci USA, 90, 4384–8.CrossRefGoogle Scholar
Mazel, D., Dychinco, B., Webb, V. A., and Davies, J. (1998). A distinctive class of integron in the Vibrio cholerae genome. Science, 280, 605–8.CrossRefGoogle ScholarPubMed
McCarthy, N. D., Colles, F. M., Dingle, K. E., et al. (2007). Population genetic approaches to assigning the source of human pathogens: host associated genetic import in Campylobacter jejuni. Emerg Infect Dis, 13, 267–72.CrossRefGoogle Scholar
McGregor, K. F., Spratt, B. G., Kalia, A., et al. (2004). Multilocus Sequence Typing of Streptococcus pyogenes representing most known emm types and distinctions among subpopulation genetic structures. J Bacteriol, 186, 4285–94.CrossRefGoogle ScholarPubMed
McVean, G., Awadalla, P., and Fearnhead, P. (2002). A coalescent-based method for detecting and estimating recombination from gene sequences. Genetics, 160, 1231–41.Google ScholarPubMed
McVean, G. A., Myers, S. R., Hunt, S., et al. (2004). The fine-scale structure of recombination rate variation in the human genome. Science, 304, 581–4.CrossRefGoogle ScholarPubMed
Milkman, R., and Bridges, M. M. (1990). Molecular evolution of the Escherichia coli chromosome. III. Clonal frames. Genetics, 126, 505–17.Google ScholarPubMed
Millman, K. L., Tavaré, S., and Dean, D. (2001). Recombination in the ompA gene but not the omcB gene of Chlamydia contributes to serovar-specific differences in tissue tropism, immune surveillance, and persistence of the organism. J Bacteriol, 183, 5997–6008.CrossRefGoogle Scholar
Modrich, P., and Lahue, R. (1996). Mismatch repair in replication fidelity, genetic recombination, and cancer biology. Annu Rev Biochem, 65, 101–33.CrossRefGoogle ScholarPubMed
Myers, S., Bottolo, L., Freeman, C., McVean, G., and Donnelly, P. (2005). A fine-scale map of recombination rates and hotspots across the human genome. Science, 310, 321–4.CrossRefGoogle ScholarPubMed
Nelson, K. E., Clayton, R. A., Gill, S. R., et al. (1999). Evidence for lateral gene transfer between Archaea and bacteria from genome sequence of Thermotoga maritima. Nature, 399, 323–9.CrossRefGoogle ScholarPubMed
Papke, R. T., Koenig, J. E., Rodriguez-Valera, F., and Doolittle, W. F. (2004). Frequent recombination in a saltern population of Halorubrum. Science, 306, 1928–9.Google Scholar
Pickard, D., Wain, J., Baker, S., et al. (2003). Composition, acquisition, and distribution of the Vi exopolysaccharide-encoding Salmonella enterica pathogenicity island SPI-7. J Bacteriol, 185, 5055–65.CrossRefGoogle ScholarPubMed
Pritchard, J., Stephens, M., and Donnelly, P. J. (2000). Inference of population structure using multilocus genotype data. Genetics, 155, 945–59.Google ScholarPubMed
Qiu, W.-G., Schutzer, S. E., Bruno, J. F., et al. (2004). Genetic exchange and plasmid transfers in Borrelia burgdorferi sensu stricto revealed by three-way genome comparisons and multilocus sequence typing. Proc Natl Acad Sci USA, 101, 14150–5.CrossRefGoogle ScholarPubMed
Recchia, G. D., and Hall, R. M. (1995). Gene cassettes: a new class of mobile element. Microbiology, 141, 3015–27.CrossRefGoogle ScholarPubMed
Robinson, D. A., and Enright, M. C. (2004). Evolution of Staphylococcus aureus by large chromosomal replacements. J Bacteriol, 186, 1060–4.CrossRefGoogle ScholarPubMed
Robinson, D. A., Briles, D. E., Crain, M. J., and Hollingshead, S. K. (2002). Evolution and virulence of serogroup 6 pneumococci on a global scale. J Bacteriol, 184, 6367–75.CrossRefGoogle ScholarPubMed
Roumagnac, P., Weill, F.-X., Dolecek, C., et al. (2006). Evolutionary history of Salmonella typhi. Science, 314, 1301–4.CrossRefGoogle ScholarPubMed
Sarkar, S. F., and Guttman, D. S. (2004). Evolution of the Core Genome of Pseudomonas syringae, a highly clonal, endemic plant pathogen. Appl Environ Microbiol, 70, 1999–2012.CrossRefGoogle ScholarPubMed
Scally, M., Schuenzel, E. L., Stouthamer, R., and Nunney, L. (2005). Multilocus Sequence Type system for the plant pathogen Xylella fastidiosa and relative contributions of recombination and point mutation to clonal diversity. Appl Environ Microbiol, 71, 8491–9.CrossRefGoogle ScholarPubMed
Schicklmaier, P., and Schmieger, H. (1995). Frequency of generalized transducing phages in natural isolates of the Salmonella typhimurium complex. Appl Environ Microbiol, 61, 1637–40.Google ScholarPubMed
Schicklmaier, P., Moser, E., Wieland, T., Rabsch, W., and Schmieger, H. (1998). A comparative study on the frequency of prophages among natural isolates of Salmonella and Escherichia coli with emphasis on generalized transducers. Antonie Van Leeuwenhoek, 73, 49–54.CrossRefGoogle ScholarPubMed
Schouls, L. M., Reulen, S., Duim, B.et al. (2003). Comparative genotyping of Campylobacter jejuni by amplified fragment length polymorphism, multilocus sequence typing, and short repeat sequencing: strain diversity, host range, and recombination. J Clin Microbiol, 41, 15–26.CrossRefGoogle Scholar
Selander, R. K., and Levin, B. R. (1980). Genetic diversity and structure in Escherichia coli populations. Science, 210, 545–7.CrossRefGoogle ScholarPubMed
Smith, G. R. (1988). Homologous recombination in procaryotes. Microbiol Rev, 52, 1–28.Google ScholarPubMed
Smith, N. H., Dale, J., Inwald, J., et al. (2003). The population structure of Mycobacterium bovis in Great Britain: clonal expansion. Proc Natl Acad Sci USA, 100, 15271–5.CrossRefGoogle ScholarPubMed
Spratt, B., Hanage, W., Li, B., Aanensen, D., and Feil, E. (2004). Displaying the relatedness among isolates of bacterial species – the eBURST approach. FEMS Microbiol Lett, 241, 129–34.CrossRefGoogle ScholarPubMed
Suerbaum, S., Smith, J. M., Bapumia, K., et al. (1998). Free recombination within Helicobacter pylori. Proc Natl Acad Sci USA, 95, 12619–24.CrossRefGoogle ScholarPubMed
Tago, Y., Imai, M., Ihara, M., et al. (2005). Escherichia coli mutator ΔpolA is defective in base mismatch correction: the nature of in vivo DNA replication errors. J Mol Biol, 351, 299–308.CrossRefGoogle Scholar
Tomb, J. F., White, O., Kerlavage, A. R., et al. (1997). The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature, 388, 539–47.CrossRefGoogle ScholarPubMed
Vulic, M., Dionisio, F.Taddei, F., and Radman, M. (1997). Molecular keys to speciation: DNA polymorphism and the control of genetic exchange in enterobacteria. Proc Natl Acad Sci USA, 94, 9763–7.CrossRefGoogle ScholarPubMed
Watterson, G. A. (1975). On the number of segregating sites in genetical models without recombination. Theor Popul Biol, 7, 256–76.CrossRefGoogle ScholarPubMed
Weinbauer, M. G. (2004). Ecology of prokaryotic viruses. FEMS Microbiol Rev, 28, 127–81.CrossRefGoogle ScholarPubMed
Whitaker, R. J., Grogan, D. W., and Taylor, J. W. (2005) Recombination shapes the natural population structure of the hyperthermophilic archaeon Sulfolobus islandicus. Mol Biol Evol, 22, 2354–61.CrossRefGoogle ScholarPubMed
Winckler, W., Myers, S. R., Richter, D. J., et al. (2005). Comparison of fine-scale recombination rates in humans and chimpanzees. Science, 308, 107–11.CrossRefGoogle ScholarPubMed
Wirth, T., Falush, D., Lan, R., et al. (2006). Sex and virulence in Escherichia coli: an evolutionary perspective. Mol Microbiol, 60, 1136–51.CrossRefGoogle Scholar
Zahrt, T. C., and Maloy, S. (1997). Barriers to recombination between closely related bacteria: MutS and RecBCD inhibit recombination between Salmonella typhimurium and Salmonella typhi. Proc Natl Acad Sci USA, 94, 9786–91.CrossRefGoogle ScholarPubMed
Zhu, P., Ende, A., Falush, D., et al. (2001). Fit genotypes and escape variants of subgroup III Neisseria meningitidis during three pandemics of epidemic meningitis. Proc Natl Acad Sci USA, 98, 15056–61.CrossRefGoogle ScholarPubMed

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