Mobile genetic elements: the agents of open source evolution

Key Points

  • Prokaryotes transfer DNA between cells by three processes: transformation, transduction and conjugation. Transduction and conjugation depend on specialized mobile genetic elements (MGEs), which include most large plasmids and certain bacteriophages (phages).

  • Prokaryotes also possess a third class of MGEs called transposons. These elements can move and rearrange chromosomal DNA in the cell. Transposons move from cell to cell through plasmids, phages, or their derivatives called integrative conjugative elements (ICEs).

  • MGEs can mediate intra- or intercellular DNA trafficking because they have unique (core or backbone) genes that allow them to replicate independently of the cellular chromosome, to engage in homologous or non-homologous recombination, and to extrude (plasmid) or package (phage) DNA for efficient movement between cells.

  • In addition to their core genes, MGEs typically carry several different accessory genes that provide their host cell with a selective advantage, such as antibiotic resistance, virulence factors, or unusual metabolic pathways. Indeed, most medically and economically important bacterial phenotypes are encoded by MGEs.

  • Although MGEs are the main agents of horizontal gene transfer (HGT), relatively few have been sequenced and analysis of their genomic and phylogenetic properties lags behind that of organismal chromosomes. Specifically, the major databases do not curate plasmid and phage nucleic acid or protein sequences. Sequencing MGE genomes presents unique challenges because phages require suitable hosts for propagation and plasmids must be physically separated from each other and from the host chromosomal DNA. The relatively small size of MGEs (5–500 kb) and their varied GC content thwart current automated annotation algorithms.

  • These challenges can be viewed as an opportunity to devise technical and bioinformatics tools for high throughput analysis of MGEs. This is important because understanding prokaryotic evolution requires knowledge of the agents that mediate this process. Such knowledge is essential for controlling problems such as the emergence of highly virulent antibiotic multi-resistant strains.

Abstract

Horizontal genomics is a new field in prokaryotic biology that is focused on the analysis of DNA sequences in prokaryotic chromosomes that seem to have originated from other prokaryotes or eukaryotes. However, it is equally important to understand the agents that effect DNA movement: plasmids, bacteriophages and transposons. Although these agents occur in all prokaryotes, comprehensive genomics of the prokaryotic mobile gene pool or 'mobilome' lags behind other genomics initiatives owing to challenges that are distinct from cellular chromosomal analysis. Recent work shows promise of improved mobile genetic element (MGE) genomics and consequent opportunities to take advantage — and avoid the dangers — of these 'natural genetic engineers'. This review describes MGEs, their properties that are important in horizontal gene transfer, and current opportunities to advance MGE genomics.

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Figure 1: Transfer of DNA between bacterial cells.
Figure 2: Signature proteins of conjugative systems in Gram-negative bacteria.
Figure 3: Genes and components of tailed phages.

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Acknowledgements

We thank M. Syvanen for the public domain software metaphor for MGEs and the reviewers for their thoughtful critiques. Work in the laboratories of R.L. and A.T. is supported by the Fonds National de la Recherche Scientifique, the Université Libre de Bruxelles, Belgium, and the European Space Agency. L.S.F. acknowledges support from the Canadian Institutes of Health Research and Natural Sciences and Engineering Research Council of Canada. A.O.S. acknowledges support from the US Department of Energy (DOE) Genomes-To-Life Program, the assistance of L. Williams, the staff of the DOE Joint Genome Institute, Walnut Creek, California and Oak Ridge National Laboratory, Tennessee.

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Correspondence to Anne O. Summers.

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DATABASES

ACLAME

Artemis

Gene Ontology

MUMmer

National Center for Biotechnology Information

Plasmid Genome Database

Swiss-Prot

VirB4

VirB10

VirB11

FURTHER INFORMATION

Laura Frost's laboratory

Raphael Leplae's laboratory

Anne Summers' laboratory

Ariane Toussaint's laboratory

Bacteriophage Names 2000

Database of Plasmid Replicons

Glossary

TRANSFORMATION

Gene transfer that is mediated by the uptake of free DNA.

CONJUGATION

Gene transfer that is mediated by certain plasmids or ICEs with relevant transfer genes. Cell–cell contact is required for conjugation, unlike transduction or transformation.

TRANSDUCTION

Gene transfer that is mediated by certain types of bacteriophage.

INTEGRATIVE CONJUGATIVE ELEMENTS

(ICEs). Together with conjugative transposons (CTns) and genomic islands, these are chromosomally located gene clusters that encode phage-linked integrases and conjugation proteins as well as other genes associated with an observable phenotype such as virulence or symbiosis. ICEs and CTns are gene clusters that can be transferred between cells, whereas genomic islands have not been shown to transfer. Although these gene clusters have some phage-like genes, they do not lyse the cell or form extracellular particles.

HOMOLOGOUS RECOMBINATION

DNA recombination that requires extensive sequence similarity in the involved DNA segments. It is usually effected by chromosomally encoded genes, but some phages also have orthologues of such chromosomal genes.

MOBILIZATION

Transfer by a conjugative element of a plasmid or part of the bacterial cellular chromosome that cannot effect self transfer. Mediated by the trans-acting proteins of the conjugative plasmid that function on cognate mobilization (oriT) sites in the mobilized plasmid to direct it to the conjugation pore built by the conjugative element.

INTEGRON

A genetic element that encodes an integrase enzyme, which can assemble tandem arrays of genes or gene fragments and provide them with a promoter for expression. Often associated with antibiotic multi-resistance.

NON-HOMOLOGOUS RECOMBINATION

DNA recombination that requires little or no similarity between the DNA segments involved. This process is carried out by specialized enzymes that are encoded by transposons and phages.

METAGENOMICS

Sequencing of a clone library derived from the total DNA purified from a complex microbial ecosystem. This is followed by computer assembly of the reads into multiple linkage groups assumed to represent the organisms present in the community, including those that cannot be cultured.

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Frost, L., Leplae, R., Summers, A. et al. Mobile genetic elements: the agents of open source evolution. Nat Rev Microbiol 3, 722–732 (2005). https://doi.org/10.1038/nrmicro1235

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