Plasmids do not consistently stabilize cooperation across bacteria but may promote broad pathogen host-range
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Abstract
Abstract Horizontal gene transfer via plasmids could favour cooperation in bacteria, because transfer of a cooperative gene turns non-cooperative cheats into cooperators. This hypothesis has received support from both theoretical and genomic analyses. In contrast, with a comparative analysis across 51 diverse species, we found that genes for extracellular proteins, which are likely to act as cooperative ‘public goods’, were not more likely to be carried on either: (i) plasmids compared to chromosomes; or (ii) plasmids that transfer at higher rates. Our results were supported by theoretical modelling which showed that while horizontal gene transfer can help cooperative genes initially invade a population, it does not favour the longer-term maintenance of cooperation. Instead, we found that genes for extracellular proteins were more likely to be on plasmids when they coded for pathogenic virulence traits, in pathogenic bacteria with a broad host-range. Taken together, these results support an alternate hypothesis, that plasmid gene location confers benefits other than horizontal gene transfer.
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The problem of non-independence can be exacerbated when examining genomes or genes.
“This problem of non-independence can be exacerbated when examining genomes or genes.”
From A phylogenetic approach to comparative genomics (2025) · cites this paper as [22]
The problem of species not being independent can be exacerbated by additional levels of non-independence, including genes within genomes and genomes of the same or closely related species.
“In genomic datasets, data points can correspond to genomes or even individual genes, meaning the problem of species not being independent can be exacerbated by additional levels of non-independence, including genes within genomes, such as those carried on the same replicon, and genomes of the same or closely related species16,19,21–26.”
From A phylogenetic approach to comparative genomics (2025) · cites this paper as [22]
Analysing genes or genomes as if they were independent data points can be equivalent to having more technical (pseudo) replicates in an experiment, but then treating each as if they were a truly independent sample (biological replicate).
“Analysing genes or genomes as if they were independent data points can be equivalent to having more technical (pseudo) replicates in an experiment, but then treating each as if they were a truly independent sample (biological replicate)22.”
From A phylogenetic approach to comparative genomics (2025) · cites this paper as [22]
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Cites
Phylogenies and the Comparative Method
Felsenstein, J. (1985) · The American Naturalist · doi:10.1086/284325 · Cited by 9,793 · see citing works
Cooperation and competition in pathogenic bacteria
Griffin, A. S., West, S. A., & Buckling, A. (2004) · Nature · doi:10.1038/nature02744 · Cited by 1,104 · see citing works
Self-citationA survey of the statistical power of research in behavioral ecology and animal behavior
Jennions, M. D. (2003) · Behavioral Ecology · doi:10.1093/beheco/14.3.438 · Cited by 278 · see citing works
Flagged first, then by citations
Research works printed but not linked: 72
- [1]Foster KR Social behaviour in microorganisms Szekely T Moore AJ Komdeur J Social Behaviour Cambridge University Press 2010 331 356 10.1017/CBO9780511781360.027 · DOI
- [2]McNally L Viana M Brown SP Cooperative secretions facilitate host range expansion in bacteria Nat Commun 2014 5 PMC4143932 25091146
- [3]West SA Griffin AS Gardner A Diggle SP Social evolution theory for microorganisms Nat Rev Microbiol 2006 4 597 607 16845430
- [4]Simonet C McNally L Kin selection explains the evolution of cooperation in the gut microbiota Proc Natl Acad Sci 2021 118 PMC8017935 33526674
- [6]Hale TL Genetic basis of virulence in Shigella species Microbiol Rev 1991 55 206 224 1886518 PMC372811
- [7]Dinges MM Orwin PM Schlievert PM Exotoxins of Staphylococcus aureus Clin Microbiol Rev 2000 13 16 34 table of contents 10627489 PMC88931
- [8]Diggle SP Griffin AS Campbell GS West SA Cooperation and conflict in quorum-sensing bacterial populations Nature 2007 450 411 414 18004383
- [9]Jones S The lux autoinducer regulates the production of exoenzyme virulence determinants in Erwinia carotovora and Pseudomonas aeruginosa EMBO J 1993 12 2477 2482 8508773 PMC413484
- [10]Sandoz KM Mitzimberg SM Schuster M Social cheating in Pseudomonas aeruginosa quorum sensing Proc Natl Acad Sci 2007 104 15876 15881 17898171 PMC2000394
- [11]Ghoul M Griffin AS West SA Toward an evolutionary definition of cheating Evolution 2014 68 318 331 24131102
- [12]Butaitė E Baumgartner M Wyder S Kümmerli R Siderophore cheating and cheating resistance shape competition for iron in soil and freshwater Pseudomonas communities Nat Commun 2017 8 414 28871205 PMC5583256
- [13]Thomas C Nielsen K Thomas CM Nielsen KM Mechanisms of, and barriers to, horizontal gene transfer between bacteria Nat Rev Micro 2005 3 711 721 Nat. Rev. Microbiol. 3, 711-21 16138099
- [14]Smith J The social evolution of bacterial pathogenesis Proc R Soc Lond B Biol Sci 2001 268 61 69 PMC1087601 12123299
- [15]Nogueira T Horizontal Gene Transfer of the Secretome Drives the Evolution of Bacterial Cooperation and Virulence Curr Biol 2009 19 1683 1691 19800234 PMC2773837
- [16]Mc Ginty SE Rankin DJ Brown SP Horizontal gene transfer and the evolution of bacterial cooperation: mobile elements and bacterial cooperation Evolution 2011 65 21 32 20825481 PMC3038327
- [17]Mc Ginty SÉ Lehmann L Brown SP Rankin DJ The interplay between relatedness and horizontal gene transfer drives the evolution of plasmid-carried public goods Proc R Soc B Biol Sci 2013 280 20130400 PMC3652439 23760639
- [18]Dimitriu T Genetic information transfer promotes cooperation in bacteria Proc Natl Acad Sci 2014 111 11103 11108 25024219 PMC4121819
- [19]Nogueira T Touchon M Rocha EPC Rapid Evolution of the Sequences and Gene Repertoires of Secreted Proteins in Bacteria PLoS ONE 2012 7 e49403 23189144 PMC3506625
- [20]Garcia-Garcera M Rocha EPC Community diversity and habitat structure shape the repertoire of extracellular proteins in bacteria Nat Commun 2020 11 758 32029728 PMC7005277
- [22]Ives AR Zhu J Statistics for correlated data: phylogenies, space, and time Ecol Appl Publ Ecol Soc Am 2006 16 20 32 16705958
- [24]Harvey PH Pagel MD The Comparative Method in Evolutionary Biology Oxford University Press 1991
- [25]Grafen A The phylogenetic regression Philos Trans R Soc Lond B Biol Sci 1989 326 119 157 2575770
- [27]Ruxton G Colegrave N Experimental Design for the Life Sciences OUP Oxford 2011
- [28]Stone GN Nee S Felsenstein J Controlling for non-independence in comparative analysis of patterns across populations within species Philos Trans R Soc B Biol Sci 2011 366 1410 1424 PMC3081573 21444315
- [29]Ives AR Midford PE Garland T Jr Within-Species Variation and Measurement Error in Phylogenetic Comparative Methods Syst Biol 2007 56 252 270 17464881
- [30]Bakkeren E Cooperative virulence can emerge via horizontal gene transfer but is stabilized by transmission bioRxiv 2021 2021.02.11.430745 10.1101/2021.02.11.430745 · DOI
- [31]Ghoul M Andersen SB West SA Sociomics: Using Omic Approaches to Understand Social Evolution Trends Genet 2017 33 408 419 28506494
- [32]McInerney JO McNally A O’Connell MJ Why prokaryotes have pangenomes Nat Microbiol 2017 2 17040 28350002
- [33]Niehus R Mitri S Fletcher AG Foster KR Migration and horizontal gene transfer divide microbial genomes into multiple niches Nat Commun 2015 6 PMC4673824 26592443
- [34]Cordero OX Ecological Populations of Bacteria Act as Socially Cohesive Units of Antibiotic Production and Resistance Science 2012 337 1228 1231 22955834
- [35]Rakoff-Nahoum S Coyne MJ Comstock LE An Ecological Network of Polysaccharide Utilization among Human Intestinal Symbionts Curr Biol 2014 24 40 49 24332541 PMC3924574
- [36]Nocelli N Bogino PC Banchio E Giordano W Roles of Extracellular Polysaccharides and Biofilm Formation in Heavy Metal Resistance of Rhizobia Materials 2016 9 418 PMC5456807 28773540
- [37]Ciofu O Beveridge TJ Kadurugamuwa J Walther-Rasmussen J Høiby N Chromosomal β-lactamase is packaged into membrane vesicles and secreted from Pseudomonas aeruginosa J Antimicrob Chemother 2000 45 9 13 10629007
- [38]Rodríguez-Beltrán J DelaFuente J León-Sampedro R MacLean RC San Millán Á Beyond horizontal gene transfer: the role of plasmids in bacterial evolution Nat Rev Microbiol 2021 1 13 10.1038/s41579-020-00497-1 33469168 · DOI
- [39]Yu NY PSORTb 3.0: improved protein subcellular localization prediction with refined localization subcategories and predictive capabilities for all prokaryotes Bioinformatics 2010 26 1608 1615 20472543 PMC2887053
- [40]Rankin DJ Rocha EPC Brown SP What traits are carried on mobile genetic elements, and why? Heredity 2011 106 1 10 20332804 PMC3183850
- [44]Crawley MJ Statistics: An Introduction Using R John Wiley & Sons 2014
- [45]Cohen J Statistical Power Analysis for the Behavioral Sciences Routledge 1988
- [46]Robertson J Nash JHE MOB-suite: software tools for clustering, reconstruction and typing of plasmids from draft assemblies Microb Genomics 2018 4 PMC6159552 30052170
- [47]Robertson J Bessonov K Schonfeld J Nash JHE Universal whole-sequence-based plasmid typing and its utility to prediction of host range and epidemiological surveillance Microb Genomics 2020 6 PMC7660255 32969786
- [48]Smillie C Garcillan-Barcia MP Francia MV Rocha EPC de la Cruz F Mobility of Plasmids Microbiol Mol Biol Rev 2010 74 434 452 20805406 PMC2937521
- [49]Mc Ginty SÉ Rankin DJ The evolution of conflict resolution between plasmids and their bacterial hosts Evolution 2012 66 1662 1670 22519798
- [50]Hamilton WD Genetical evolution of social behaviour I & II J Theor Biol 1964 7 1 52 5875341
- [52]Ghigo JM Natural conjugative plasmids induce bacterial biofilm development Nature 2001 412 442 445 11473319
- [53]Di Venanzio G Multidrug-resistant plasmids repress chromosomally encoded T6SS to enable their dissemination Proc Natl Acad Sci U S A 2019 116 1378 1383 30626645 PMC6347727
- [54]Sheppard RJ Beddis AE Barraclough TG The role of hosts, plasmids and environment in determining plasmid transfer rates: A meta-analysis Plasmid 2020 108 102489 31926878
- [55]Rodríguez-Beltrán J Genetic dominance governs the evolution and spread of mobile genetic elements in bacteria Proc Natl Acad Sci 2020 117 15755 15762 32571917 PMC7355013
- [56]Cornelis GR The Virulence Plasmid of Yersinia, an Antihost Genome Microbiol Mol Biol Rev 1998 62 1315 1352 9841674 PMC98948
- [57]Köstlbacher S Collingro A Halter T Domman D Horn M Coevolving Plasmids Drive Gene Flow and Genome Plasticity in Host-Associated Intracellular Bacteria Curr Biol 2021 31 346 357 e3 33157023 PMC7846284
- [58]Gupta A Kapil R Dhakan DB Sharma VK MP3: A Software Tool for the Prediction of Pathogenic Proteins in Genomic and Metagenomic Data PLOS ONE 2014 9 e93907 24736651 PMC3988012
- [59]San Millan A Escudero JA Gifford DR Mazel D MacLean RC Multicopy plasmids potentiate the evolution of antibiotic resistance in bacteria Nat Ecol Evol 2017 1 0010 28812563
- [60]Carrier T Jones KL Keasling JD mRNA stability and plasmid copy number effects on gene expression from an inducible promoter system Biotechnol Bioeng 1998 59 666 672 10099386
- [61]Rodríguez-Beltrán J Multicopy plasmids allow bacteria to escape from fitness trade-offs during evolutionary innovation Nat Ecol Evol 2018 2 873 881 29632354 PMC6055991
- [62]Dietel A-K Kaltenpoth M Kost C Convergent Evolution in Intracellular Elements: Plasmids as Model Endosymbionts Trends Microbiol 2018 26 755 768 29650391
- [63]Rocha EPC Danchin A Base composition bias might result from competition for metabolic resources Trends Genet 2002 18 291 294 12044357
- [64]Hug LA A new view of the tree of life Nat Microbiol 2016 1 16048 27572647
- [65]Garcia-Garcera M Touchon M Brisse S Rocha EPC Metagenomic assessment of the interplay between the environment and the genetic diversification of Acinetobacter Environ Microbiol 2017 19 5010 5024 28967182 PMC5767740
- [66]Kümmerli R Schiessl KT Waldvogel T McNeill K Ackermann M Habitat structure and the evolution of diffusible siderophores in bacteria Ecol Lett 2014 17 1536 1544 25250530
- [67]Canchaya C Fournous G Chibani-Chennoufi S Dillmann ML Brüssow H Phage as agents of lateral gene transfer Curr Opin Microbiol 2003 6 417 424 12941415
- [68]Burrus V Waldor MK Shaping bacterial genomes with integrative and conjugative elements Res Microbiol 2004 155 376 386 15207870
- [69]O’Brien FG Origin-of-transfer sequences facilitate mobilisation of non-conjugative antimicrobial-resistance plasmids in Staphylococcus aureus Nucleic Acids Res 2015 43 7971 7983 26243776 PMC4652767
- [70]Rodríguez-Rubio L Extensive antimicrobial resistance mobilization via multicopy plasmid encapsidation mediated by temperate phages J Antimicrob Chemother 2020 75 3173 3180 32719862 PMC7566468
- [71]Ramsay JP Firth N Diverse mobilization strategies facilitate transfer of non-conjugative mobile genetic elements Curr Opin Microbiol 2017 38 1 9 28391142
- [72]Jain R Rivera MC Lake JA Horizontal gene transfer among genomes: the complexity hypothesis Proc Natl Acad Sci U S A 1999 96 3801 3806 10097118 PMC22375
- [73]Cohen O Gophna U Pupko T The complexity hypothesis revisited: connectivity rather than function constitutes a barrier to horizontal gene transfer Mol Biol Evol 2011 28 1481 1489 21149642
- [74]Ding W Baumdicker F Neher RA panX: pan-genome analysis and exploration Nucleic Acids Res 2018 46 e5 29077859 PMC5758898
- [75]Gardy JL Brinkman FSL Methods for predicting bacterial protein subcellular localization Nat Rev Microbiol 2006 4 741 751 16964270
- [76]Ference CM Recent advances in the understanding of Xanthomonas citri ssp. citri pathogenesis and citrus canker disease management Mol Plant Pathol 2018 19 1302 1318 29105297 PMC6638175
- [80]Nakagawa S Johnson PCD Schielzeth H The coefficient of determination R2 and intra-class correlation coefficient from generalized linear mixed-effects models revisited and expanded J R Soc Interface 2017 11 PMC5636267 28904005
- [81]Paradis E Schliep K ape 5.0: an environment for modern phylogenetics and evolutionary analyses in R Bioinforma Oxf Engl 2019 35 526 528 30016406
- [83]Washburne AD Methods for phylogenetic analysis of microbiome data Nat Microbiol 2018 3 652 661 29795540
- [84]Som A Causes, consequences and solutions of phylogenetic incongruence Brief Bioinform 2015 16 536 548 24872401
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- Authors
- Dewar, A. E., Thomas, J. L., Scott, T. W., Wild, G., Griffin, A. S., West, S. A., & Ghoul, M.
- Affiliations
- University of Oxford (GB)
- Western University (CA)
- Corresponding author
- Dewar, Anna E.
- ORCID
- Venue
- Nature Ecology & Evolution
- Published
- 2021-11-08
- Volume
- 5
- Issue
- 12
- Pages
- 1624-1636
- ISSN
- 2397-334X (ISSN-L)
- PMC
- PMC7612097
- OpenAlex
- W3190432843
- Cited by
- 44
- References
- 3
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 8 · 2023: 11 · 2022: 8 · 2021: 4
- FWCI
- 9.85
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Nature Ecology & Evolution (publishedVersion)
- Research Square (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Oxford University Research Archive (ORA) (University of Oxford) (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Natural Sciences and Engineering Research Council of Canada
- Biotechnology and Biological Sciences Research Council (BB/M011224/1)
- Natural Environment Research Council (NE/V011537/1)
- Topics
- Social Sciences › Sociology and Political Science › Evolutionary Game Theory and Cooperation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- plasmids, horizontal gene transfer, cooperation, public goods, extracellular proteins, virulence genes, host range, pathogenic bacteria, bacterial evolution, comparative genomics
- MeSH terms
- Bacteria, Plasmids, Gene Transfer, Horizontal, Host Specificity
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