An IS-mediated, RecA-dependent, bet-hedging strategy in Burkholderia thailandensis
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Curated by eLife
eLife assessment
This paper reports a bet hedging strategy in bacteria based on chromosomal duplications and rearrangements that confer advantages in certain growth conditions. The work is of fundamental importance for understanding the role of genetic and biological variation in bacteria. The experimental work is exceptionally strong and convincing. The paper will be of interest to a broad audience including bacteriologists, geneticists and evolutionary biologists.
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Abstract
Adaptation to fluctuating environmental conditions is difficult to achieve. Phase variation mechanisms can overcome this difficulty by altering genomic architecture in a subset of individuals, creating a phenotypically heterogeneous population with subpopulations optimized to persist when conditions change, or are encountered, suddenly. We have identified a phase variation system in Burkholderia thailandensis that generates a genotypically and phenotypically heterogeneous population. Genetic analyses revealed that RecA-mediated homologous recombination between a pair of insertion sequence (IS) 2 -like elements duplicates a 208.6 kb region of DNA that contains 157 coding sequences. RecA-mediated homologous recombination also resolves merodiploids, and hence copy number of the region is varied and dynamic within populations. We showed that the presence of two or more copies of the region is advantageous for growth in a biofilm, and a single copy is advantageous during planktonic growth. While IS elements are well known to contribute to evolution through gene inactivation, polar effects on downstream genes, and altering genomic architecture, we believe that this system represents a rare example of IS element-mediated evolution in which the IS elements provide homologous sequences for amplification of a chromosomal region that provides a selective advantage under specific growth conditions, thereby expanding the lifestyle repertoire of the species.
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eLife assessment
This paper reports a bet hedging strategy in bacteria based on chromosomal duplications and rearrangements that confer advantages in certain growth conditions. The work is of fundamental importance for understanding the role of genetic and biological variation in bacteria. The experimental work is exceptionally strong and convincing. The paper will be of interest to a broad audience including bacteriologists, geneticists and evolutionary biologists.
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Reviewer #1 (Public Review):
This is an exceptional paper that investigates a 208.6 kb region of the Burkholderia thailandensis chromosome that had previously been thought to excise itself and form extrachromosomal circles. Through a series of elegant experiments , the authors conclusively show that (i) the 208.6 kb region in fact forms tandem duplications, (ii) the region can switch between duplicated and non-duplicated forms via RecA-mediated homologous recombination, and (iii) duplication provides a selective advantage in biofilms. The data are of uniformly high quality and the conclusions are fully supported by the data. The significance of the work is high because it identifies a novel form of phase variation in bacteria that represents a bet-hedging strategy to facilitate growth in diverse environments.
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Reviewer #2 (Public Review):
This beautiful study identifies a genetic mechanism controlling colony morphology differences in Burkholderia thailandensis. There is a large region of the genome which can be duplicated or triplicated in a RecA-dependent recombination process, leading to phenotypic changes. In addition to colony morphology differences in cells with one, two, or three copies of the region, other phenotypes like biofilm formation are impacted. This appears to be an unstable genetic change since some of the colony types can interconvert to others after restreaking. The authors are commended for the development of elegant genetic approaches to study and carefully prove the existence of the copy number variation of this genomic region. These approaches will be of great use to the field in studying copy number variation in …
Reviewer #2 (Public Review):
This beautiful study identifies a genetic mechanism controlling colony morphology differences in Burkholderia thailandensis. There is a large region of the genome which can be duplicated or triplicated in a RecA-dependent recombination process, leading to phenotypic changes. In addition to colony morphology differences in cells with one, two, or three copies of the region, other phenotypes like biofilm formation are impacted. This appears to be an unstable genetic change since some of the colony types can interconvert to others after restreaking. The authors are commended for the development of elegant genetic approaches to study and carefully prove the existence of the copy number variation of this genomic region. These approaches will be of great use to the field in studying copy number variation in bacteria far beyond Burkholderia or colony morphology/biofilm formation. Bacteriology has for decades focused on average measurements of a culture, and this study helps usher the field to a new future where we appreciate and measure the behaviors of individual populations of cells within the same culture.
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Reviewer #3 (Public Review):
This paper shows that RecA-mediated recombination between two insertion sequence elements can drive the duplication of a large (~200 kb) region that leads to a growth advantage in biofilms, but a disadvantage during planktonic growth. The experiments presented are incisive and definitive. While IS elements are more commonly implicated in gene inactivation, this paper reveals that they can provide a benefit by driving a reversible genome modification in the form of a large-scale duplication. The paper should appeal to readers interested in mechanisms of genome evolution, phase variation, biofilms, and bacterial pathogenesis. The final model is convincing and also lays the foundation for future studies aimed at identifying which gene(s) in the duplicated region are ultimately responsible for the biofilm growth …
Reviewer #3 (Public Review):
This paper shows that RecA-mediated recombination between two insertion sequence elements can drive the duplication of a large (~200 kb) region that leads to a growth advantage in biofilms, but a disadvantage during planktonic growth. The experiments presented are incisive and definitive. While IS elements are more commonly implicated in gene inactivation, this paper reveals that they can provide a benefit by driving a reversible genome modification in the form of a large-scale duplication. The paper should appeal to readers interested in mechanisms of genome evolution, phase variation, biofilms, and bacterial pathogenesis. The final model is convincing and also lays the foundation for future studies aimed at identifying which gene(s) in the duplicated region are ultimately responsible for the biofilm growth benefit. The paper also serves to correct this lab's prior interpretation of related data in which they concluded that the genomic region being investigated excised and circularized. They very nicely lay out what led them to conclude this previously and how their new data led to a revised model, as well as many additional, important new insights. To be clear, there were no issues with the prior data, just the interpretation/model. So in my view, this is exactly how science should unfold - new data can and should lead to revised models. I applaud the authors for laying this trajectory out in such a straightforward, open manner.
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