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Cited by 92Bacterial Genetics and BiotechnologyBacteriophages and microbial interactionsCRISPR and Genetic Engineering

Restriction-modification systems have shaped the evolution and distribution of plasmids across bacteria

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Shaw, Liam P, Rocha, Eduardo P C, MacLean, R Craig·2023·Nucleic Acids Research
DOI 10.1093/nar/gkad452PMC PMC10359461

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Abstract

Many novel traits such as antibiotic resistance are spread by plasmids between species. Yet plasmids have different host ranges. Restriction-modification systems (R-M systems) are by far the most abundant bacterial defense system and therefore represent one of the key barriers to plasmid spread. However, their effect on plasmid evolution and host range has been neglected. Here we analyse the avoidance of targets of the most abundant R-M systems (Type II) for complete genomes and plasmids across bacterial diversity. For the most common target length (6 bp) we show that target avoidance is strongly correlated with the taxonomic distribution of R-M systems and is greater in plasmid genes than core genes. We find stronger avoidance of R-M targets in plasmids which are smaller and have a broader host range. Our results suggest two different evolutionary strategies for plasmids: small plasmids primarily adapt to R-M systems by tuning their sequence composition, and large plasmids primarily adapt through the carriage of additional genes protecting from restriction. Our work provides systematic evidence that R-M systems are important barriers to plasmid transfer and have left their mark on plasmids over long evolutionary time.

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  • More recently developed methods allow analyses to go further and test competing causal hypotheses.

    “More recently developed methods allow analyses to go further and test competing causal hypotheses42,84.”

    From A phylogenetic approach to comparative genomics (2025) · cites this paper as [84]

    The Materials and Methods sections describe a developed pipeline for predicting R-M targets, a sequence-composition null model, and phylogenetically controlled analyses. These methods support the point that analyses can go further, but the paper does not present them as a general advance for testing competing causal hypotheses. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • Causal inference methods such as phylogenetic path analysis could be used to test causal hypotheses.

    “In this case, causal inference methods such as phylogenetic path analysis could be used to test causal hypotheses84,88,89.”

    From A phylogenetic approach to comparative genomics (2025) · cites this paper as [84]

    The Materials and Methods section, “Modelling palindrome avoidance controlling for phylogeny” (page unavailable), describes a phylogenetically controlled model of R-M target avoidance. It does not discuss phylogenetic path analysis or propose causal-inference methods for testing causal hypotheses. Searches for those terms found no supporting passage in our copy. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Shaw, L. P., Rocha, E. P. C., & MacLean, R. C.
Affiliations
  • Durham University (GB)
  • Centre National de la Recherche Scientifique (FR)
  • University of Oxford (GB)
Corresponding author
Shaw, Liam P
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2023-05-31
Volume
51
Issue
13
Pages
6806-6818
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkad452
PMC
PMC10359461
OpenAlex
W4378783055
Cited by
92
References
0
Citations by year
2026: 32 · 2025: 36 · 2024: 22 · 2023: 2
FWCI
14.62
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Durham Research Online (Durham University) (publishedVersion, other-oa)
  • Oxford University Research Archive (ORA) (University of Oxford) (acceptedVersion, cc-by)
  • HAL (submittedVersion, cc-by)
  • Durham Research Online (Durham University) (submittedVersion, cc-by)
Funders
  • Wellcome (220422/Z/20/Z, 106918/Z/15Z, 203141/Z/16/Z)
  • Fondation pour la Recherche Médicale (EQU201903007835)
  • Integrative Biology of Emerging Infectious Diseases (ANR-10-LABX-62-IBEID)
  • NIHR Oxford BR
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Physical Sciences › Environmental Science › Ecology › Bacteriophages and microbial interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
Keywords
restriction-modification systems, plasmids, plasmid evolution, host range, bacterial defense mechanisms, plasmid size, horizontal gene transfer, bacterial taxonomy
MeSH terms
Adaptation, Physiological, Bacteria, Drug Resistance, Microbial, Plasmids, DNA Restriction-Modification Enzymes

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