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Beyond horizontal gene transfer: the role of plasmids in bacterial evolution

Abstract

Plasmids have a key role in bacterial ecology and evolution because they mobilize accessory genes by horizontal gene transfer. However, recent studies have revealed that the evolutionary impact of plasmids goes above and beyond their being mere gene delivery platforms. Plasmids are usually kept at multiple copies per cell, producing islands of polyploidy in the bacterial genome. As a consequence, the evolution of plasmid-encoded genes is governed by a set of rules different from those affecting chromosomal genes, and these rules are shaped by unusual concepts in bacterial genetics, such as genetic dominance, heteroplasmy or segregational drift. In this Review, we discuss recent advances that underscore the importance of plasmids in bacterial ecology and evolution beyond horizontal gene transfer. We focus on new evidence that suggests that plasmids might accelerate bacterial evolution, mainly by promoting the evolution of plasmid-encoded genes, but also by enhancing the adaptation of their host chromosome. Finally, we integrate the most relevant theoretical and empirical studies providing a global understanding of the forces that govern plasmid-mediated evolution in bacteria.

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Fig. 1: Plasmid prevalence and types.
Fig. 2: Evolutionary forces that drive the evolution of plasmid-encoded genes.
Fig. 3: The role of genetic dominance in plasmid evolution.

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Acknowledgements

This work was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC grant agreement 757440-PLASREVOLUTION) and by the Instituto de Salud Carlos III (grant PI16-00860) co-funded by European Regional Development Fund “A way to achieve Europe”. Á.S.M. is supported by a Miguel Servet Fellowship (MS15-00012). J.R.-B. is a recipient of a Juan de la Cierva-Incorporación Fellowship (IJC2018-035146-I) co-funded by Agencia Estatal de Investigación del Ministerio de Ciencia e Innovación. R.C.M. is supported by a Wellcome Trust grant (106918/Z/15/Z). Á.S.M, J.R.-B. and R.L.-S. are members of the Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP).

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All authors contributed substantially to the conceptualization and writing of the manuscript, which was originally conceived and drafted by J.R.-B. and Á.S.M.

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Correspondence to Jerónimo Rodríguez-Beltrán or Álvaro San Millán.

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Nature Reviews Microbiology thanks T. Dagan, E. Koonin, and E. Top, who co-reviewed with S. Castaneda Barba and C. Elg, for their contribution to the peer review of this work.

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Glossary

Horizontal gene transfer

(HGT). Transfer of genetic material between cells that do not share an ancestor–descendant relationship.

Postsegregational killing systems

Genetic systems that ensure plasmid maintenance. They typically rely on the production of a long-lasting toxin and a short-lived antitoxin. If the plasmid is lost in a daughter cell, the antitoxin is rapidly degraded and the stable toxin kills the plasmid-free cell.

Compensatory evolution

Process by which the fitness cost produced by the acquisition of a plasmid is ameliorated through mutations in the chromosome and/or the plasmid.

Second-order selection

Process by which evolution, while directly selecting for adaptive genetic variability, indirectly selects for the system that created that variability.

Type IV CRISPR–Cas systems

Recently characterized CRISPR–Cas systems found predominantly on plasmids and that primarily target other plasmids. Type IV CRISPR–Cas systems are thus believed to have a role in mediating interplasmid competition.

Plasmid segregation

Physical separation of plasmid molecules to be inherited by daughter cells during cell division.

Gene dosage effects

Effect by which the phenotype of a given mutation is proportional to the cumulative number of mutant alleles present in the cell.

Tandem genetic duplications

Duplication of a region of DNA adjacent to the original one.

Bet-hedging

Stochastic process by which some individuals in a community are better suited to tackle environmental perturbations, usually at the price of a reduced growth rate in the short term.

Recombination

Exchange of genetic information between two distinct DNA molecules.

Mutator strains

Strains that permanently show unusually high mutation rates due to a malfunction of a DNA repair mechanism.

Transposable elements

DNA sequences that can move within genomes by a cut-and-paste mechanism.

Heteroplasmy

Coexistence of two different plasmids sharing the same nucleotide sequences for all regions involved in the replication and maintenance system within the same cell. Cells carrying plasmids under heteroplasmy are dubbed ‘heteroplasmid cells’, whereas cells carrying a unique version of a plasmid are termed ‘homoplasmid cells’.

Genetic drift

Change in allele frequency in a population due to random sampling.

Clonal interference

Competition between cellular lineages in a population arising from different beneficial mutations in asexually reproducing organisms.

Standing genetic variation

The presence of more than one allele at a locus in a population before environmental change.

Trade-offs

In evolution, trade-offs are negative correlations between ancestral and novel traits.

SOS stress response

Coordinated cellular response to genotoxic stress that involves the expression of more than 40 genes whose main function is to repair damaged DNA.

Integron

Genetic element composed by an integrase gene and a recombination site in which gene cassettes can be directionally integrated or excised by integrase-mediated site-specific recombination.

Epistatic interactions

Phenomenon by which the phenotypic contribution of a gene varies depending on the presence or absence of another gene. The phenotypic effect of both genes in combination is thus different from the effect expected according to the phenotypes they conferred separately.

Purifying selection

Selective pressure that eliminates deleterious alleles from populations.

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Rodríguez-Beltrán, J., DelaFuente, J., León-Sampedro, R. et al. Beyond horizontal gene transfer: the role of plasmids in bacterial evolution. Nat Rev Microbiol (2021). https://doi.org/10.1038/s41579-020-00497-1

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