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  Evolutionary rescue and drug resistance on multicopy plasmids

Santer, M., & Uecker, H. (2020). Evolutionary rescue and drug resistance on multicopy plasmids. Genetics, 215(2). doi:10.1534/genetics.119.303012.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0006-3E06-F Version Permalink: http://hdl.handle.net/21.11116/0000-0006-9C7C-0
Genre: Journal Article

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 Creators:
Santer, Mario1, Author              
Uecker, Hildegard1, Author              
Affiliations:
1Research Group Stochastic Evolutionary Dynamics, Department Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_2640692              

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Free keywords: rapid adaptation; antibiotic resistance; bacterial evolution; plasmid copy number; dominance
 Abstract: Bacteria often carry "extra DNA" in form of plasmids in addition to their chromosome. Many plasmids have a copy number greater than one such that the genes encoded on these plasmids are present in multiple copies per cell. This has evolutionary consequences by increasing the mutational target size, by prompting the (transitory) co-occurrence of mutant and wild-type alleles within the same cell, and by allowing for gene dosage effects. We develop and analyze a mathematical model for bacterial adaptation to harsh environmental change if adaptation is driven by beneficial alleles on multicopy plasmids. Successful adaptation depends on the availability of advantageous alleles and on their establishment probability. The establishment process involves the segregation of mutant and wild-type plasmids to the two daughter cells, allowing for the emergence of mutant-homozygous cells over the course of several generations. To model this process, we use the theory of multi-type branching processes, where a type is defined by the genetic composition of the cell. Both factors - the availability of advantageous and their establishment probability - depend on the plasmid copy number, and they often do so antagonistically. We find that in the interplay of various effects, a lower or higher copy number may maximize the probability of evolutionary rescue. The decisive factor is the dominance relationship between mutant and wild-type plasmids and potential gene dosage effects. Results from a simple model of antibiotic degradation indicate that the optimal plasmid copy number may depend on the specific environment encountered by the population.

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Language(s): eng - English
 Dates: 2020-05-142019-12-232020-05-152019-12-232020-06
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: No review
 Identifiers: DOI: 10.1534/genetics.119.303012
 Degree: -

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Title: Genetics
Source Genre: Journal
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Publ. Info: Genetics Society of America
Pages: - Volume / Issue: 215 (2) Sequence Number: - Start / End Page: - Identifier: ISSN: 0016-6731
CoNE: https://pure.mpg.de/cone/journals/resource/954925400554