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Effect of the translesion DNA polymerases, endonucleases and RpoS on mutation rates in Salmonella typhimurium
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. (Dan Andersson)
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology. (Diarmaid Hughes)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. (Dan Andersson)
2010 (English)In: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 185, no 3, 783-795 p.Article in journal (Refereed) Published
Abstract [en]

It has been suggested that bacteria have evolved mechanisms to increase their mutation rate in response to various stresses and that the translesion DNA polymerase Pol IV under control of the LexA regulon and the alternative sigma factor RpoS are involved in regulating this mutagenesis. Here we examined in Salmonella enterica serovar Typhimurium LT2 the rates for four different types of mutations (rifampicin-, nalidixic acid- and chlorate-resistance and Lac+ reversion) during various growth conditions and with different levels of four translesion DNA polymerases (Pol II, Pol IV, Pol V and SamAB) and RpoS. Constitutive de-repression of the LexA regulon by a lexA(def) mutation increased mutation rates 1.5- to 12-fold and the contribution of the translesion DNA polymerases to this mutagenesis varied with the type of mutation examined. In contrast, for all four types of mutations examined the increase in mutation rate in the lexA(def) mutant required the presence of the LexA-controlled endonucleases UvrB, UvrC and Cho. With regard to the potential involvement of RpoS in mutagenesis, neither an increase in RpoS levels conferred by artificial over-expression from a plasmid nor long-term stationary phase incubation or slow growth caused an increase in any of the four mutation rates measured, alone or in combination with over-expression of the translesion DNA polymerases. In conclusion, mutation rates are remarkably robust and no combination of growth conditions, induction of translesion polymerases by inactivation of LexA or increased RpoS expression could confer an increase in mutation rates higher than the moderate increase caused by de-repression of the LexA regulon alone.

Place, publisher, year, edition, pages
2010. Vol. 185, no 3, 783-795 p.
Keyword [en]
bacteria, stress, mutation
National Category
Medical and Health Sciences
Research subject
Evolutionary Genetics; Microbiology
Identifiers
URN: urn:nbn:se:uu:diva-111426DOI: 10.1534/genetics.110.116376ISI: 000281906800007PubMedID: 20421601OAI: oai:DiVA.org:uu-111426DiVA: diva2:281152
Available from: 2009-12-14 Created: 2009-12-14 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Dynamics of the Bacterial Genome: Rates and Mechanisms of Mutation
Open this publication in new window or tab >>Dynamics of the Bacterial Genome: Rates and Mechanisms of Mutation
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Bacterial chromosomes are highly dynamic, continuously changing with respect to gene content and size via a number of processes, including deletions that result in gene loss. How deletions form and at what rates has been the focus of this thesis.

In paper II we investigated how chromosomal location affects chromosomal deletion rates in S. typhimurium. Deletion rates varied more than 100-fold between different chromosomal locations and some large deletions significantly increased the exponential growth rate of the cells. Our results suggest that the chromosome is heterogeneous with respect to deletion rates and that deletions may be genetically fixed as a consequence of natural selection rather than by drift or mutational biases.

In paper I we examined in a laboratory setting how rapidly reductive evolution, i.e. gene loss, could occur. Using a serial passage approach, we showed that extensive genome reduction potentially could occur on a very short evolutionary time scale. For most deletions we observed little or no homology at the deletion endpoints, indicating that spontaneous deletions often form through a RecA independent process.

In paper III we examined further how large spontaneous deletions form and, unexpectedly, showed that 90% of all spontaneous chromosomal deletions required error-prone translesion DNA polymerases for their formation. We propose that the translesion polymerases stimulate deletion formation by allowing extension of misaligned single-strand DNA ends.

In paper IV we investigated how the translesion DNA polymerase Pol IV, RpoS and different types of stresses affect mutation rates in bacteria. Derepression of the LexA regulon caused a small to moderate increase in mutation rates that was fully dependent on functional endonucleases but only partly dependent on translesion DNA polymerases. RpoS levels and growth stresses had only minor effects on mutation rates. Thus, mutation rates appear very robust and are only weakly affected by growth conditions and induction of translesion polymerases and RpoS.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 56 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 509
Keyword
bacteria, bacterial evolution, genome reduction, gene loss, serial passage, DNA homology, tranlesion DNA polymerase, stress
National Category
Microbiology in the medical area Microbiology in the medical area
Research subject
Evolutionary Genetics; Microbiology
Identifiers
urn:nbn:se:uu:diva-111428 (URN)978-91-554-7687-8 (ISBN)
Public defence
2010-02-05, C10:305, BMC, Husargatan 3, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2010-01-14 Created: 2009-12-14 Last updated: 2010-01-15

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Koskiniemi, SannaHughes, DiarmaidAndersson, Dan I

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