Copy Number Change: Evolving views on Gene Amplification

Elliott, Kathryn T.; Cuff, Laura E.; Neidle, Ellen L.

doi:10.2217/fmb.13.53

Cited by 65 publications

(61 citation statements)

References 83 publications

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“…Alternatively, the changes might be explained by gene amplification. Gene amplification is a proven mechanism for evolution and acquisition of new gene product functions that includes the adaptation of genes acquired by horizontal gene transfer (Elliott et al ., ), and antibiotic resistance (Reams and Neidle, 2003; 2004; Seaton et al ., ; Elliott et al ., ). Such changes are usually unstable and difficult to detect (Andersson and Hughes, ), however they allow bacteria to increase the chance of acquiring mutations (Bergthorsson et al ., ; Andersson and Hughes, ; Nasvall et al ., ).…”

Section: Discussionmentioning

confidence: 99%

Activation of phenotypic subpopulations in response to ciprofloxacin treatment in Acinetobacter baumannii

MacGuire

Ching

Diamond

et al. 2014

Molecular Microbiology

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Summary The multidrug-resistant, opportunistic pathogen, Acinetobacter baumannii, has spread swiftly through hospitals worldwide. Previously, we demonstrated that A. baumannii regulates the expression of various genes in response to DNA damage. Some of these regulated genes, especially those encoding the multiple error-prone DNA polymerases, can be implicated in induced mutagenesis, leading to antibiotic resistance. Here, we further explore the DNA damage-inducible system at the single cell level using chromosomal transcriptional reporters for selected DNA damage response genes. We found the genes examined respond in a bimodal fashion to ciprofloxacin treatment, forming two phenotypic subpopulations: induced and uninduced. This bimodal response to ciprofloxacin treatment in A. baumannii is unique and quite different than the Escherichia coli paradigm. The subpopulations are not genetically different, with each subpopulation returning to a starting state and differentiating with repeated treatment. We then identified a palindromic motif upstream of certain DNA damage response genes, and have shown alterations to this sequence to diminish the bimodal induction in response to DNA damaging treatment. Lastly, we are able to show a biological advantage for a bimodal response, finding that one subpopulation survives ciprofloxacin treatment better than the other.

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Section: Discussionmentioning

confidence: 99%

Activation of phenotypic subpopulations in response to ciprofloxacin treatment in Acinetobacter baumannii

MacGuire

Ching

Diamond

et al. 2014

Molecular Microbiology

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“…Adaptation by increased gene expression can result from mutations of different types (Blank et al, 2014; Lind et al, 2015): point mutations, promoter insertion by mobile elements (Mahillon and Chandler, 1998; Ellison and Bachtrog, 2013; Stoebel et al, 2009), promoter capture by chromosomal rearrangements (ar-Rushdi et al, 1983; Blount et al, 2012; Xiao et al, 2008), and gene duplication or amplification, which increases expression by way of gene dosage (Andersson and Hughes, 2009; Elliott et al, 2013). How the rate of mutation of these individual mutation types depends on chromosomal position has in part been determined experimentally (Foster et al, 2013; Hudson et al, 2002; Mahillon and Chandler, 1998; Craig, 1997; Touchon et al, 2009; Anderson and Roth, 1981; Seaton et al, 2012; Wahl et al, 1984).…”

Section: Introductionmentioning

confidence: 99%

Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection

Steinrueck

Guet

2017

eLife

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How the organization of genes on a chromosome shapes adaptation is essential for understanding evolutionary paths. Here, we investigate how adaptation to rapidly increasing levels of antibiotic depends on the chromosomal neighborhood of a drug-resistance gene inserted at different positions of the Escherichia coli chromosome. Using a dual-fluorescence reporter that allows us to distinguish gene amplifications from other up-mutations, we track in real-time adaptive changes in expression of the drug-resistance gene. We find that the relative contribution of several mutation types differs systematically between loci due to properties of neighboring genes: essentiality, expression, orientation, termination, and presence of duplicates. These properties determine rate and fitness effects of gene amplification, deletions, and mutations compromising transcriptional termination. Thus, the adaptive potential of a gene under selection is a system-property with a complex genetic basis that is specific for each chromosomal locus, and it can be inferred from detailed functional and genomic data.DOI: http://dx.doi.org/10.7554/eLife.25100.001

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“…Most points in the bacterial chromosome are not flanked by extensive repeats and give rise to duplications whose junctions have short sequence repeats (4 -12 base pairs) that are presumed to arise by some kind of single-strand annealing, template switching, or nonhomologous end joining. Several complex models suggest how junctions with short (or absent) repeated sequences can be generated by a multistep process (Hastings et al 2009b;Kugelberg et al 2010;Brewer et al 2011;Elliott et al 2013). In the absence of extensive repeats, duplications may form by aberrant recombination activities of topoisomerases (Shyamala et al 1990).…”

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confidence: 99%