1887

Abstract

The pangenome contains all genes encoded by a species, with the core genome present in all strains and the accessory genome in only a subset. Coincident gene relationships are expected within the accessory genome, where the presence or absence of one gene is influenced by the presence or absence of another. Here, we analysed the accessory genome of an pangenome consisting of 400 genomes from 20 sequence types to identify genes that display significant co-occurrence or avoidance patterns with one another. We present a complex network of genes that are either found together or that avoid one another more often than would be expected by chance, and show that these relationships vary by lineage. We demonstrate that genes co-occur by function, and that several highly connected gene relationships are linked to mobile genetic elements. We find that genes are more likely to co-occur with, rather than avoid, another gene in the accessory genome. This work furthers our understanding of the dynamic nature of prokaryote pangenomes and implicates both function and mobility as drivers of gene relationships.

Funding
This study was supported by the:
  • h2020 marie skłodowska-curie actions (Award 793818)
    • Principle Award Recipient: FionaJ Whelan
  • wellcome trust (Award Wellcome Midas DTP)
    • Principle Award Recipient: ChristopherConnor
  • wellcome trust (Award Wellcome AAMR DTP)
    • Principle Award Recipient: ElizabethA Cummins
  • biotechnology and biological sciences research council (Award BB/N018044/2)
    • Principle Award Recipient: JamesO McInerney
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2021-09-09
2024-04-24
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References

  1. Goodall ECA, Robinson A, Johnston IG, Jabbari S, Turner KA et al. The essential genome of Escherichia coli K-12. mBio 2018; 9:02096–17 [View Article]
    [Google Scholar]
  2. Pang TY, Lercher MJ. Each of 3,323 metabolic innovations in the evolution of E. coli arose through the horizontal transfer of a single DNA segment. Proc Natl Acad Sci U S A 2019; 116:187–192 [View Article] [PubMed]
    [Google Scholar]
  3. Domingo-Sananes MR, McInerney JO. Mechanisms that shape microbial pangenomes. Trends Microbiol 2021; 29:493–503 [View Article]
    [Google Scholar]
  4. Ogura Y, Ooka T, Iguchi A, Toh H, Asadulghani M et al. Comparative genomics reveal the mechanism of the parallel evolution of O157 and non-O157 enterohemorrhagic Escherichia coli. Proc Natl Acad Sci U S A 2009; 106:17939–17944 [View Article]
    [Google Scholar]
  5. Hentschel U, Hacker J. Pathogenicity islands: The tip of the iceberg. Microbes Infect 2001; 3:545–548 [View Article] [PubMed]
    [Google Scholar]
  6. Johnson TJ. Separate F-type plasmids have shaped the evolution of the H30 subclone of Escherichia coli sequence type 131. mSphere 2016; 1:00121–16
    [Google Scholar]
  7. Nakamura K, Murase K, Sato MP, Toyoda A, Itoh T et al. Differential dynamics and impacts of prophages and plasmids on the pangenome and virulence factor repertoires of Shiga toxin-producing Escherichia coli O145:H28. Microb Genom 2020; 6: [View Article] [PubMed]
    [Google Scholar]
  8. Bruns H, Crüsemann M, Letzel A-C, Alanjary M, McInerney JO et al. Function-related replacement of bacterial siderophore pathways. ISME J 2018; 12:320–329 [View Article]
    [Google Scholar]
  9. Rasko DA, Rosovitz MJ, Myers GSA, Mongodin EF, Fricke WF et al. The pangenome structure of Escherichia coli: Comparative genomic analysis of E. coli commensal and pathogenic isolates. J Bacteriol 2008; 190:6881–6893 [View Article] [PubMed]
    [Google Scholar]
  10. Dobrindt U. Patho-)Genomics of Escherichia coli. Int J Med Microbiol 2005; 295:357–371 [View Article] [PubMed]
    [Google Scholar]
  11. Decano AG, Downing T. An Escherichia coli ST131 pangenome atlas reveals population structure and evolution across 4,071 isolates. Sci Rep 2019; 9:17394 [View Article]
    [Google Scholar]
  12. Chen SL, Hung C-S, Xu J, Reigstad CS, Magrini V et al. Identification of genes subject to positive selection in uropathogenic strains of Escherichia coli: A comparative genomics approach. Proc Natl Acad Sci U S A 2006; 103:5977–5982 [View Article] [PubMed]
    [Google Scholar]
  13. Whelan FJ, Rusilowicz M, McInerney JO. Coinfinder: Detecting significant associations and dissociations in pangenomes. Microbial Genomics 2020; 6:e000338 [View Article]
    [Google Scholar]
  14. Seemann T. PROKKA: Rapid prokaryotic genome annotation. Bioinformatics 2014; 30:2068–2069 [View Article] [PubMed]
    [Google Scholar]
  15. Tonkin-Hill G, MacAlasdair N, Ruis C, Weimann A, Horesh G et al. Producing polished prokaryotic pangenomes with the Panaroo pipeline. Genome Biol 2020; 21:180 [View Article] [PubMed]
    [Google Scholar]
  16. Capella-Gutiérrez S, Silla-Martínez JM, Gabaldón T. trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses. Bioinformatics 2009; 25:1972–1973 [View Article] [PubMed]
    [Google Scholar]
  17. Nguyen L-T, Schmidt HA, von Haeseler A, Minh BQ. IQ-TREE: A fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. Mol Biol Evol 2015; 32:268–274 [View Article]
    [Google Scholar]
  18. Abadi S, Azouri D, Pupko T, Mayrose I. Model selection may not be a mandatory step for phylogeny reconstruction. Nat Commun 2019; 10:934 [View Article] [PubMed]
    [Google Scholar]
  19. Letunic I, Bork P. Interactive Tree of Life (iTOL) v4: Recent updates and new developments. Nucleic Acids Res 2019; 47:W256–W259 [View Article]
    [Google Scholar]
  20. Whelan FJ, Hall RJ, McInerney JO. Evidence for selection in the abundant accessory gene content of a prokaryote pangenome. Mol Biol Evol 2021 [View Article]
    [Google Scholar]
  21. The UniProt Consortium UNIPROT: The universal protein knowledge base. Nucleic Acids Research 2017; 45:
    [Google Scholar]
  22. Kanehisa M, Goto S. KEGG: Kyoto Encyclopedia of Genes and Genomes. Tech Rep 2000; 1:
    [Google Scholar]
  23. Caspi R, Altman T, Billington R, Dreher K, Foerster H et al. The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of Pathway/Genome Databases. Nucleic Acids Res 2014; 42:D459–71 [View Article]
    [Google Scholar]
  24. Arredondo-Alonso S, Rogers MRC, Braat JC, Verschuuren TD, Top J et al. mlplasmids: a user-friendly tool to predict plasmid- and chromosome-derived sequences for single species. Microb Genom 2018; 4:e000224 [View Article] [PubMed]
    [Google Scholar]
  25. Page AJ, Cummins CA, Hunt M, Wong VK, Reuter S et al. Roary: Rapid large-scale prokaryote pan genome analysis. Bioinformatics 2015; 31:3691–3693 [View Article] [PubMed]
    [Google Scholar]
  26. Kawasaki Y, Wada C, Yura T. Roles of Escherichia coli heat shock proteins DnaK, DnaJ and GrpE in mini-F plasmid replication. Molec Gen Genet 1990; 220:277–282 [View Article]
    [Google Scholar]
  27. Makino K, Ishii K, Yasunaga T, Hattori M, Yokoyama K et al. Complete nucleotide sequences of 93-kb and 3.3-kb plasmids of an enterohemorrhagic Escherichia coli O157:H7 derived from Sakai outbreak. DNA Res 1998; 5:1–9 [View Article] [PubMed]
    [Google Scholar]
  28. Schmidt H, Beutin L, Karch H. Molecular analysis of the plasmid-encoded hemolysin of Escherichia coli O157:H7 strain EDL 933. Infect Immun 1995; 63:1055–1061 [View Article] [PubMed]
    [Google Scholar]
  29. Waldor MK. Bacteriophage biology and bacterial virulence. Trends Microbiol 1998; 6:295–297 [View Article] [PubMed]
    [Google Scholar]
  30. Handa N, Kobayashi I. Type III Restriction Is Alleviated by Bacteriophage (RecE) Homologous Recombination Function but Enhanced by Bacterial (RecBCD) Function. J Bacteriol 2005; 187:7362–7373 [View Article] [PubMed]
    [Google Scholar]
  31. Bachler C, Schneider P, Bahler P, Lustig A, Erni B. Escherichia coli dihydroxyacetone kinase controls gene expression by binding to transcription factor DhaR. EMBO J 2005; 24:283–293 [View Article] [PubMed]
    [Google Scholar]
  32. Jenkins LS, Nunn WD. Genetic and molecular characterization of the genes involved in short-chain fatty acid degradation in Escherichia coli: The ATO system. J Bacteriol 1987; 169:42–52 [View Article] [PubMed]
    [Google Scholar]
  33. Rome K, Borde C, Taher R, Cayron J, Lesterlin C et al. The two-component system ZRAPSR is a novel ESR that contributes to intrinsic antibiotic tolerance in Escherichia coli. J Mol Biol 2018; 430:4971–4985 [View Article] [PubMed]
    [Google Scholar]
  34. Francetic O, Belin D, Badaut C, Pugsley AP. Expression of the endogenous type II secretion pathway in Escherichia coli leads to chitinase secretion. EMBO Journal 2000; 19:6697–6703 [View Article]
    [Google Scholar]
  35. Miki T, Okada N, Kim Y, Abe A, Danbara H. DsbA directs efficient expression of outer membrane secretin EscC of the enteropathogenic Escherichia coli type III secretion apparatus. Microb Pathog 2008; 44:151–158 [View Article] [PubMed]
    [Google Scholar]
  36. Silver RP, Aaronson W, Vann WF. The K1 capsular polysaccharide of Escherichia coli. Rev Infect Dis 1988; 10 Suppl 2:S282–6 [View Article]
    [Google Scholar]
  37. Postma PW, Lengeler JW. Phosphoenolpyruvate: Carbohydrate phosphotransferase system of bacteria; 1985
  38. Tchieu JH, Norris V, Edwards JS, Saier MH. The complete phosphotransferase system in Escherichia coli. J Mol Microbiol Biotechnol 2001; 3:329–346 [PubMed]
    [Google Scholar]
  39. Manges AR, Geum HM, Guo A, Edens TJ, Fibke CD et al. Global extraintestinal pathogenic Escherichia coli (ExPEC) lineages. Clin Microbiol Rev 2019; 32: [View Article]
    [Google Scholar]
  40. Sokurenko EV, Chesnokova V, Dykhuizen DE, Ofek I, Wu XR et al. Pathogenic adaptation of Escherichia coli by natural variation of the FIMH adhesin. Proc Natl Acad Sci U S A 1998; 95:8922–8926 [View Article]
    [Google Scholar]
  41. McNally A. Diversification of colonization factors in a multidrug-resistant Escherichia coli lineage evolving under negative frequency- dependent selection. mBio 2019; 10:00644–19
    [Google Scholar]
  42. Rousset F. The impact of genetic diversity on gene essentiality within the E. coli species. bioRxiv 2020
    [Google Scholar]
  43. McInerney JO, McNally A, O’Connell MJ. Why prokaryotes have pangenomes. Nature Microbiology 2017; 2:1–5
    [Google Scholar]
  44. Shapiro BJ. The population genetics of pangenomes; 2017
  45. Andreani NA, Hesse E, Vos M. Prokaryote genome fluidity is dependent on effective population size. ISME Journal 2017; 11:1719–1721 [View Article]
    [Google Scholar]
  46. Lu Q-F, Cao D-M, Su L-L, Li S-B, Ye G-B et al. Genus-wide comparative genomics analysis of Neisseria to identify new genes associated with pathogenicity and niche adaptation of Neisseria pathogens. Int J Genomics 2019; 2019:6015730 [View Article]
    [Google Scholar]
  47. Didelot X, Wilson DJ. Clonalframeml: Efficient inference of recombination in whole bacterial genomes. PLoS Comput Biol 2015; 11:e1004041 [View Article] [PubMed]
    [Google Scholar]
  48. Cusumano CK, Hung CS, Chen SL, Hultgren SJ. Virulence plasmid harbored by uropathogenic Escherichia coli functions in acute stages of pathogenesis. Infect Immun 2010; 78:1457–1467 [View Article] [PubMed]
    [Google Scholar]
  49. Kuenne C. Reassessment of the Listeria monocytogenes pan-genome reveals dynamic integration hotspots and mobile genetic elements as major components of the accessory genome. BMC Genomics 2013; 14:47 [View Article] [PubMed]
    [Google Scholar]
  50. Firth N, Skurray R. Characterization of the F plasmid bifunctional conjugation gene, traG. MGG Molecular & General Genetics 1992; 232:145–153
    [Google Scholar]
  51. Wallden K, Rivera-Calzada A, Waksman G. Type IV secretion systems: Versatility and diversity in function; 2010
  52. Schmidt H, Henkel B, Karch H. A gene cluster closely related to type II secretion pathway operons of Gram-negative bacteria is located on the large plasmid of enterohemorrhagic Escherichia coli O157 strains. FEMS Microbiology Letters 2006; 148:265–272 [View Article]
    [Google Scholar]
  53. Arciszewska L, Sherratt D. Xer site-specific recombination in vitro. EMBO J 1995; 14:2112–2120 [PubMed]
    [Google Scholar]
  54. Cornet F, Hallet B, Sherratt DJ. Xer recombination in Escherichia coli: Site-specific DNA topoisomerase activity of the XerC and XerD recombinases. Journal of Biological Chemistry 1997; 272:21927–21931
    [Google Scholar]
  55. Denamur E, Clermont O, Bonacorsi S, Gordon D. The population genetics of pathogenic Escherichia coli. Nat Rev Microbiol 2020; 19:37–54 [View Article] [PubMed]
    [Google Scholar]
  56. Brockhurst MA, Harrison E, Hall JPJ, Richards T, McNally A et al. The ecology and evolution of pangenomes. Current Biology 2019; 29:R1094–R1103 [View Article]
    [Google Scholar]
  57. Zhang X. First identification of coexistence of blaNDM-1 and bla CMY42 among Escherichia coli ST167 clinical isolates. BMC Microbiol 2013; 13:282 [View Article] [PubMed]
    [Google Scholar]
  58. Schaufler K. Genomic and functional analysis of emerging virulent and multidrug-resistant Escherichia coli lineage sequence type 648. Antimicrob Agents Chemother 2019; 63: [View Article] [PubMed]
    [Google Scholar]
  59. Hibbing ME, Dodson KW, Kalas V, Chen SL, Hultgren SJ. Adaptation of arginine synthesis among uropathogenic branches of the Escherichia coli phylogeny reveals adjustment to the urinary tract habitat. mBio 2020; 11: [View Article]
    [Google Scholar]
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