Evolving promiscuously

Andersson, Dan I.

doi:10.1073/pnas.1018588108

Cited by 7 publications

(6 citation statements)

References 22 publications

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“…Upregulation of a designated gene via promoter mutation is estimated to be 5 to 8 orders of magnitude less frequent than GDA of the same gene (55,56). We do not know the mechanism of acquiring the nuh promoter mutation associated with variants A and B, but it is striking that a single nuh allele is present in all variants.…”

Section: Discussionmentioning

confidence: 90%

Gene Duplication in Pseudomonas aeruginosa Improves Growth on Adenosine

et al. 2017

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The laboratory strain of , PAO1, activates genes for catabolism of adenosine using quorum sensing (QS). However, this strain is not well-adapted for growth on adenosine, with doubling times greater than 40 h. We previously showed that when PAO1 is grown on adenosine and casein, variants emerge that grow rapidly on adenosine. To understand the mechanism by which this adaptation occurs, we performed whole-genome sequencing of five isolates evolved for rapid growth on adenosine. All five genomes had a gene duplication-amplification (GDA) event covering several genes, including the quorum-regulated nucleoside hydrolase gene,, and PA0148, encoding an adenine deaminase. In addition, two of the growth variants also exhibited a promoter mutation. We recapitulated the rapid growth phenotype with a plasmid containing six genes common to all the GDA events. We also showed that and PA0148, the two genes at either end of the common GDA, were sufficient to confer rapid growth on adenosine. Additionally, we demonstrated that the variant promoter increased basal expression of but maintained its QS regulation. Therefore, GDA in confers the ability to grow efficiently on adenosine while maintaining QS regulation of nucleoside catabolism. thrives in many habitats and is an opportunistic pathogen of humans. In these diverse environments, must adapt to use myriad potential carbon sources. PAO1 cannot grow efficiently on nucleosides, including adenosine; however, it can acquire this ability through genetic adaptation. We show that the mechanism of adaptation is by amplification of a specific region of the genome and that the amplification preserves the regulation of the adenosine catabolic pathway by quorum sensing. These results demonstrate an underexplored mechanism of adaptation by , with implications for phenotypes such as development of antibiotic resistance.

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Section: Discussionmentioning

confidence: 90%

Gene Duplication in Pseudomonas aeruginosa Improves Growth on Adenosine

et al. 2017

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“…It can be speculated that antibiotic‐resistant mutants might present a fitness gain in the presence of sublethal antibiotic concentrations (Andersson & Hughes, 2011). Importantly, subinhibitory antibiotic concentrations might also contribute to the emergence of resistance via gene duplication, according to the gene‐duplication‐amplification model (Andersson & Hughes, 2009; Andersson, 2011) mentioned before. The frequency of tandem gene duplications may be thousands of times higher than the frequency of spontaneous mutations.…”

Section: Undesirable Effects Of Subinhibitory Antibiotic Concentrationsmentioning

confidence: 99%

Emergence and spread of antibiotic resistance following exposure to antibiotics

Cantón¹,

Morosini²

2011

FEMS Microbiol Rev

287

162

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Within a susceptible wild-type population, a small fraction of cells, even <10(-9) , is not affected when challenged by an antimicrobial agent. This subpopulation has mutations that impede antimicrobial action, allowing their selection during clinical treatment. Emergence of resistance occurs in the frame of a selective compartment termed a mutant selection window (MSW). The lower margin corresponds to the minimum inhibitory concentration of the susceptible cells, whereas the upper boundary, named the mutant prevention concentration (MPC), restricts the growth of the entire population, including that of the resistant mutants. By combining pharmacokinetic/pharmacodynamic concepts and an MPC strategy, the selection of resistant mutants can be limited. Early treatment avoiding an increase of the inoculum size as well as a regimen restricting the time within the MSW can reduce the probability of emergence of the resistant mutants. Physiological and, possibly, genetic adaptation in biofilms and a high proportion of mutator clones that may arise during chronic infections influence the emergence of resistant mutants. Moreover, a resistant population can emerge in a specific selective compartment after acquiring a resistance trait by horizontal gene transfer, but this may also be avoided to some extent when the MPC is reached. Known linkage between antimicrobial use and resistance should encourage actions for the design of antimicrobial treatment regimens that minimize the emergence of resistance. Emergence of a resistant bacterial subpopulation within a susceptible wild-type population can be restricted with a regimen using an antibiotic dose that is sufficiently high to inhibit both susceptible and resistant bacteria.

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“…An increase in gene dosage through genetic duplication and amplification (GDA) is a common process that allows rapid adaptation to variable, limiting or extreme conditions (Reams and Neidle, 2004a; Andersson and Hughes, 2009; Andersson, 2011). GDA not only plays a key role in evolution and chromosomal organization, but it also underlies medical issues ranging from chemotherapeutic resistance and cancer to developmental, cognitive and autoimmune disorders (Albertson, 2006; Conrad and Antonarakis, 2007; Craven and Neidle, 2007; Stankiewicz and Lupski, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…This dynamic nature motivates recent mathematical models of evolutionary processes to incorporate transient intermediate states of amplified DNA (Pettersson et al ., 2009; Innan and Kondrashov, 2010). In Escherichia coli and Salmonella enterica serovar Typhimurium, GDA has emerged as a central theme in efforts to assess mutation rates during bacterial adaptation to growth‐limiting conditions (Reams et al ., 2010; Andersson, 2011; Pranting and Andersson, 2011; Roth, 2011). Such studies demonstrate how novel phenotypes emerge rapidly due to population heterogeneity since many cells (approximately 10%) typically carry a duplication of some region of the chromosome.…”

Section: Introductionmentioning

confidence: 99%

Genome‐wide selection for increased copy number in Acinetobacter baylyi ADP1: locus and context‐dependent variation in gene amplification

Seaton

Elliott

Cuff

et al. 2011

Molecular Microbiology

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SummaryRenewed interest in gene amplification stems from its importance in evolution and a variety of medical problems ranging from drug resistance to cancer. However, amplified DNA segments (amplicons) are not fully characterized in any organism. Here we report a novel Acinetobacter baylyi system for genome-wide studies. Amplification mutants that consume aromatic compounds were selected under conditions requiring high-level expression from three promoters in a linked set of chromosomal genes. Tools were developed to relocate these catabolic genes to any non-essential chromosomal position, and 49 amplification mutants from five genomic contexts were characterized. Amplicon size (18-271 kb) and copy number (2-105) indicated that 30% of mutants carried more than 1 Mb of amplified DNA. Amplification features depended on genomic position. For example, amplicons from one locus were similarly sized but displayed variable copy number, whereas those from another locus were differently sized but had comparable copy number. Additionally, the importance of sequence context was highlighted in one region where amplicons differed depending on the presence of a promoter mutation in the strain from which they were selected. DNA sequences at amplicon boundaries in 19 mutants reflected illegitimate recombination. Furthermore, steady-state duplication frequencies measured under non-selective conditions (10 -4 to 10 -5) confirmed that spontaneous gene duplication is a major source of genetic variation.

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Evolving promiscuously

Cited by 7 publications

References 22 publications

Gene Duplication in Pseudomonas aeruginosa Improves Growth on Adenosine

Gene Duplication in Pseudomonas aeruginosa Improves Growth on Adenosine

Emergence and spread of antibiotic resistance following exposure to antibiotics

Genome‐wide selection for increased copy number in Acinetobacter baylyi ADP1: locus and context‐dependent variation in gene amplification

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