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Why prokaryotes have pangenomes

Nature Microbiology volume 2, Article number: 17040 (2017) Cite this article

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The existence of large amounts of within-species genome content variability is puzzling. Population genetics tells us that fitness effects of new variants—either deleterious, neutral or advantageous—combined with the long-term effective population size of the species determines the likelihood of a new variant being removed, spreading to fixation or remaining polymorphic. Consequently, we expect that selection and drift will reduce genetic variation, which makes large amounts of gene content variation in some species so puzzling. Here, we amalgamate population genetic theory with models of horizontal gene transfer and assert that pangenomes most easily arise in organisms with large long-term effective population sizes, as a consequence of acquiring advantageous genes, and that the focal species has the ability to migrate to new niches. Therefore, we suggest that pangenomes are the result of adaptive, not neutral, evolution.

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Figure 1: Schematic representation of pangenomes as Venn diagrams.
Figure 2: Analysis of accessory gene functions in 228 E. coli ST131 genomes.

References

  1. Perna, N. T. et al. Genome sequence of enterohaemorrhagic Escherichia coli O157:H7. Nature 409, 529–533 (2001).

    Article  CAS  Google Scholar 

  2. Young, J. P. et al. The genome of Rhizobium leguminosarum has recognizable core and accessory components. Genome Biol. 7, R34 (2006).

    Article  Google Scholar 

  3. Tettelin, H. et al. Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial “pan-genome”. Proc. Natl. Acad. Sci. USA 102, 13950–13955 (2005).

    Article  CAS  Google Scholar 

  4. Ku, C. et al. Endosymbiotic gene transfer from prokaryotic pangenomes: inherited chimerism in eukaryotes. Proc. Natl Acad. Sci. USA 112, 10139–10146 (2015).

    Article  CAS  Google Scholar 

  5. Treangen, T. J. & Rocha, E. P. Horizontal transfer, not duplication, drives the expansion of protein families in prokaryotes. PLoS Genet. 7, e1001284 (2011).

    Article  CAS  Google Scholar 

  6. Martinez-Murcia, A. J., Benlloch, S. & Collins, M. D. Phylogenetic interrelationships of members of the genera Aeromonas and Plesiomonas as determined by 16S ribosomal DNA sequencing: lack of congruence with results of DNA-DNA hybridizations. Int. J. Syst. Bacteriol. 42, 412–421 (1992).

    Article  CAS  Google Scholar 

  7. Creevey, C. J. et al. Does a tree-like phylogeny only exist at the tips in the prokaryotes? Proc. R. Soc. Lond. B 271, 2551–2558 (2004).

    Article  CAS  Google Scholar 

  8. Doolittle, W. F. Phylogenetic classification and the universal tree. Science 284, 2124–2129 (1999).

    Article  CAS  Google Scholar 

  9. Daubin, V., Moran, N. A. & Ochman, H. Phylogenetics and the cohesion of bacterial genomes. Science 301, 829–832 (2003).

    Article  CAS  Google Scholar 

  10. Bapteste, E. et al. Evolutionary analyses of non-genealogical bonds produced by introgressive descent. Proc. Natl Acad. Sci. USA 109, 18266–18272 (2012).

    Article  CAS  Google Scholar 

  11. Land, M. et al. Insights from 20 years of bacterial genome sequencing. Funct. Integr. Genomics 15, 141–161 (2015).

    CAS  Google Scholar 

  12. Lukjancenko, O., Wassenaar, T. M. & Ussery, D. W. Comparison of 61 sequenced Escherichia coli genomes. Microb. Ecol. 60, 708–720 (2010).

    Article  CAS  Google Scholar 

  13. Lapierre, P. & Gogarten, J. P. Estimating the size of the bacterial pan-genome. Trends Genet. 25, 107–110 (2009).

    Article  CAS  Google Scholar 

  14. Li, R. et al. Building the sequence map of the human pan-genome. Nat. Biotechnol. 28, 57–63 (2010).

    Article  CAS  Google Scholar 

  15. Ku, C. et al. Endosymbiotic origin and differential loss of eukaryotic genes. Nature 524, 427–432 (2015).

    Article  CAS  Google Scholar 

  16. Lynch, M. & Conery, J. S. The origins of genome complexity. Science 302, 1401–1404 (2003).

    Article  CAS  Google Scholar 

  17. Shapiro, B. J. How clonal are bacteria over time? Curr. Opin. Microbiol. 31, 116–123 (2016).

    Article  Google Scholar 

  18. Vos, M., Hesselman, M. C., te Beek, T. A., van Passel, M. W. & Eyre-Walker, A. Rates of lateral gene transfer in prokaryotes: high but why? Trends Microbiol. 23, 598–605 (2015).

    Article  CAS  Google Scholar 

  19. Kimura, M. The Neutral Theory of Molecular Evolution (Cambridge Univ. Press, 1984).

    Google Scholar 

  20. Lane, N. & Martin, W. The energetics of genome complexity. Nature 467, 929–934 (2010).

    Article  CAS  Google Scholar 

  21. Ohta, T. Slightly deleterious mutant substitutions in evolution. Nature 246, 96–98 (1973).

    Article  CAS  Google Scholar 

  22. Konstantinidis, K. T. & Tiedje, J. M. Trends between gene content and genome size in prokaryotic species with larger genomes. Proc. Natl Acad. Sci. USA 101, 3160–3165 (2004).

    Article  CAS  Google Scholar 

  23. Kuo, C. H. & Ochman, H. Deletional bias across the three domains of life. Genome Biol. Evol. 1, 145–152 (2009).

    Article  Google Scholar 

  24. Sela, I., Wolf, Y. I. & Koonin, E. V. Theory of prokaryotic genome evolution. Proc. Natl Acad. Sci. USA 113, 11399–11407 (2016).

    Article  CAS  Google Scholar 

  25. Nakamura, Y., Itoh, T., Matsuda, H. & Gojobori, T. Biased biological functions of horizontally transferred genes in prokaryotic genomes. Nat. Genet. 36, 760–766 (2004).

    Article  CAS  Google Scholar 

  26. Pandey, D. P. & Gerdes, K. Toxin-antitoxin loci are highly abundant in free-living but lost from host-associated prokaryotes. Nucleic Acids Res. 33, 966–976 (2005).

    Article  CAS  Google Scholar 

  27. McNally, A. et al. Combined analysis of variation in core, accessory and regulatory genome regions provides a super-resolution view into the evolution of bacterial populations. PLoS Genet. 12, e1006280 (2016).

    Article  Google Scholar 

  28. Baltrus, D. A. Exploring the costs of horizontal gene transfer. Trends Ecol. Evol. 28, 489–495 (2013).

    Article  Google Scholar 

  29. Charlesworth, B. Fundamental concepts in genetics: effective population size and patterns of molecular evolution and variation. Nat. Rev. Genet. 10, 195–205 (2009).

    Article  CAS  Google Scholar 

  30. Niehus, R., Mitri, S., Fletcher, A. G. & Foster, K. R. Migration and horizontal gene transfer divide microbial genomes into multiple niches. Nat. Commun. 6, 8924 (2015).

    Article  CAS  Google Scholar 

  31. Karcagi, I. et al. Indispensability of horizontally transferred genes and its impact on bacterial genome streamlining. Mol. Biol. Evol. 33, 1257–1269 (2016).

    Article  CAS  Google Scholar 

  32. Hutchison, C. A. 3rd et al. Design and synthesis of a minimal bacterial genome. Science 351, aad6253 (2016).

    Article  Google Scholar 

  33. Chang, Y. J. et al. Non-contiguous finished genome sequence and contextual data of the filamentous soil bacterium Ktedonobacter racemifer type strain (SOSP1–21). Stand. Genomic Sci. 5, 97–111 (2011).

    Article  CAS  Google Scholar 

  34. Lee, M. C. & Marx, C. J. Repeated, selection-driven genome reduction of accessory genes in experimental populations. PLoS Genet. 8, e1002651 (2012).

    Article  CAS  Google Scholar 

  35. Locey, K. J. & Lennon, J. T. Scaling laws predict global microbial diversity. Proc. Natl Acad. Sci. USA 113, 5970–5975 (2016).

    Article  CAS  Google Scholar 

  36. Erwin, D. H. A public goods approach to major evolutionary innovations. Geobiology 13, 308–315 (2015).

    Article  CAS  Google Scholar 

  37. McInerney, J. O., Pisani, D., Bapteste, E. & O'Connell, M. J. The public goods hypothesis for the evolution of life on Earth. Biol. Direct 6, 41 (2011).

    Article  Google Scholar 

  38. Schatz, M. C. et al. Whole genome de novo assemblies of three divergent strains of rice, Oryza sativa, document novel gene space of aus and indica. Genome Biol. 15, 506 (2014).

    PubMed  PubMed Central  Google Scholar 

  39. Li, Y. H. et al. De novo assembly of soybean wild relatives for pan-genome analysis of diversity and agronomic traits. Nat. Biotechnol. 32, 1045–1052 (2014).

    Article  CAS  Google Scholar 

  40. Read, B. A. et al. Pan genome of the phytoplankton Emiliania underpins its global distribution. Nature 499, 209–213 (2013).

    Article  CAS  Google Scholar 

  41. Ding, W., Baumdicker, F. & Neher, R. A. panX: pan-genome analysis and exploration. Preprint at bioRxivhttps://doi.org/10.1101/072082 (2016).

  42. Sharp, P. M., Stenico, M., Peden, J. F. & Lloyd, A. T. Codon usage: mutational bias, translational selection, or both? Biochem. Soc. Trans. 21, 835–841 (1993).

    Article  CAS  Google Scholar 

  43. McInerney, J. O. Replicational and transcriptional selection on codon usage in Borrelia burgdorferi. Proc. Natl Acad. Sci. USA 95, 10698–10703 (1998).

    Article  CAS  Google Scholar 

  44. McInerney, J. O. Prokaryotic genome evolution as assessed by multivariate analysis of codon usage patterns. Microb. Comp. Genomics 2, 89–97 (1997).

    Article  CAS  Google Scholar 

  45. Doherty, A. & McInerney, J. O. Translational selection frequently overcomes genetic drift in shaping synonymous codon usage patterns in vertebrates. Mol. Biol. Evol. 30, 2263–2267 (2013).

    Article  CAS  Google Scholar 

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Acknowledgements

We wish to thank J. Mallet for commenting on a draft of this manuscript. We would also like to thanks the anonymous reviewers. J.O.M. is funded by BBSRC grant no. BB/N018044/1 and the John Templeton Foundation.

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Authors and Affiliations

  1. Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, M13 9PL, UK

    James O. McInerney

  2. Institute of Microbiology and Infection, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, B15 2TT, Birmingham, UK

    Alan McNally

  3. Computational and Molecular Evolutionary Biology Group, School of Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK

    Mary J. O'Connell

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  1. James O. McInerney
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J.O.M., A.M. and M.J.O. collectively conceived and wrote this manuscript.

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Correspondence to James O. McInerney.

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McInerney, J., McNally, A. & O'Connell, M. Why prokaryotes have pangenomes. Nat Microbiol 2, 17040 (2017). https://doi.org/10.1038/nmicrobiol.2017.40

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