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Mechanisms of, and Barriers to, Horizontal Gene Transfer between Bacteria

Key Points

  • Mutation and horizontal gene transfer (HGT) continually give rise to new bacterial genotypes. Infrequently, such new bacterial genotypes establish and spread in the larger population through either positive selection or random genetic drift. Therefore, bacterial genomes are in a constant state of flux, and any segment of DNA in a large bacterial population might have the opportunity to be horizontally transferred.

  • Three main mechanisms of HGT have been described: natural transformation, the uptake of free DNA in competent bacteria, exhibited by about 1% of validly described bacterial species; transduction, the transfer of bacterial DNA between a bacteriophage-infected bacterium and a bacteriophage-susceptible bacterium; and conjugation, the transfer of mobile genetic elements by pili structures assembled between two adjacently located bacteria.

  • A number of factors limit the transfer, uptake and stabilization of foreign DNA molecules acquired by bacteria. These include limited release and stability of adaptive DNA in the environment; limits on competence development; limits on host range of the transfer and maintenance mechanism of mobile genetic elements; recipient restriction enzyme activity; and limited ability of foreign DNA to integrate into a replicating genetic element owing to a lack of DNA sequence similarity.

  • Homologous recombination depends on the incoming DNA containing regions between 25 and 200 bp in length, depending on the system, of high similarity to the recipient genome. Dependence on DNA sequence similarity for recombination between species is relaxed in some mutator strains. DNA acquisition through double-stranded breaks and end-joining — illegitimate recombination — applies more to integration of circular DNA than linear fragments.

  • Most of the understanding of the processes facilitating HGT and their frequencies of occurrence have come from well designed laboratory studies of a few model bacterial species. These studies have proven suited to resolve the basic biological mechanisms involved, but fail to encompass the environmental variables involved. We have still to develop a quantitative and qualitative understanding of ongoing gene-transfer processes occurring under natural conditions. Biologically significant gene-transfer processes might occur at temporospatial scales that current methodology do not allow us to monitor.

Abstract

Bacteria evolve rapidly not only by mutation and rapid multiplication, but also by transfer of DNA, which can result in strains with beneficial mutations from more than one parent. Transformation involves the release of naked DNA followed by uptake and recombination. Homologous recombination and DNA-repair processes normally limit this to DNA from similar bacteria. However, if a gene moves onto a broad-host-range plasmid it might be able to spread without the need for recombination. There are barriers to both these processes but they reduce, rather than prevent, gene acquisition.

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Figure 1: The process of horizontal gene transfer.
Figure 2: The natural transformation of recipient bacteria and selection of transformants.
Figure 3: Overview of plasmids and conjugative transfer in the horizontal spread of genes.

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Acknowledgements

Current work related to this review in the laboratory of C.M.T. is supported by The Wellcome Trust, INTAS, BBSRC and the Darwin Trust of Edinburgh. K.M.N. acknowledge support from The Research Council of Norway.

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DATABASES

Entrez

Bacillus subtilis

Neisseria gonorrheae

Escherichia coli

Haemophilus influenzae

Pseudomonas putida

Pseudomonas syringae

Rms149

RSF1010

Staphylococcus aureus

Streptococcus pneumoniae

FURTHER INFORMATION

Christopher Thomas' homepage

Kaare Nielsen's homepage

Glossary

COMPETENCE

The ability of bacteria to take up extracellular DNA.

TRANSFORMATION FREQUENCY

The number of bacteria carrying the horizontally acquired DNA divided by the total number of bacteria exposed, per given time unit.

HOMOLOGOUS RECOMBINATION

Recombination that depends on extensive segments of high sequence similarity between two DNA molecules.

INSERTION SEQUENCE

A transposable DNA segment that normally only encodes the enzymes that mediate its own transposition and has no phenotypic marker.

TRANSPOSASE

The enzyme that promotes cutting the DNA at the ends of a transposable element and joining to the DNA molecule into which the element is to be inserted.

PHAGE

An abbreviation of bacteriophage — a virus that specifically infects bacteria.

SPECIALIZED TRANSDUCING PHAGE

A bacteriophage that integrates into a host-cell chromosome and then is excised again, bringing with it (as part of the phage genome) part of the host chromosome that can be transferred across to a new host.

PILUS

The proteinaceous fibre made from multiple subunits of a protein called pilin that mediates contact between donor and recipient bacteria prior to conjugative transfer.

PHEROMONE

A diffusible small molecule that can act as a chemical signal.

HYPHAE

The tube-like cellular growth associated with mycelial organisms.

MOBILIZATION

The process of a non-self-transmissible element being allowed to tranfer by the presence of a self-transmissible element.

RELAXASOME

The protein–DNA complex at the transfer origin that results in nicking of the DNA when the proteins are denatured chemically or cleaved proteolytically.

SURFACE EXCLUSION

The reduction of transfer frequency during conjugative transfer to recipients already carrying a related plasmid.

PARALOGUES

Homologous genes in the same organism that have evolved from a gene duplication and a subsequent divergence of function.

ORTHOLOGUES

Homologues that are related to each other through a speciation event.

HELICASE

Enzyme that unwinds DNA duplexes.

LAGGING-STRAND SYNTHESIS

Discontinuous synthesis on the strand running back from the replication fork, dependent on regular synthesis of primers by a primase and other primosome proteins.

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Thomas, C., Nielsen, K. Mechanisms of, and Barriers to, Horizontal Gene Transfer between Bacteria. Nat Rev Microbiol 3, 711–721 (2005). https://doi.org/10.1038/nrmicro1234

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