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Variation in spontaneous deletion rates at different locations of the Salmonella typhimurium chromosome
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. (Dan Andersson)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. (Dan Andersson)
(English)Manuscript (preprint) (Other (popular science, discussion, etc.))
Abstract [en]

How and at what rates spontaneous deletions form is still a partly unresolved question. Here we have constructed a genetic tool that can be used to determine spontaneous chromosomal deletion rates at any chromosomal location. We measured deletion rates at 12 chromosomal locations and identified the deletable region as the largest deletion found at each location. Our data shows that spontaneous deletion rates can at least vary 100-fold between the different chromosomal locations when normalized to the size of the deletable region. The isolated deletions ranged in size from 1-200 kbp and the highest deletion rates were found around 2 Mbp of the S. typhiumurium chromosome, suggesting a potential hotspot for deletion formation. No long repeat sequences were found in this region that could explain the high deletion rate. Furthermore, no obvious correlation between fitness (measured as exponential growth rate) and deletion size could be seen. Surprisingly, since deletions are commonly considered deleterious certain deletions (ranging from 18- to 38 kbp in size) increased the growth rate of the cells with ~5% in both rich and poor growth media. These results suggest that the bacterial chromosome is heterogeneous with respect to the rate of deletion formation and that some deletions could become fixed as a consequence of natural selection rather than by drift and/or mutational biases.

Keyword [en]
bacteria, gene loss, chromosome
National Category
Microbiology in the medical area Microbiology in the medical area
Research subject
Evolutionary Genetics; Microbiology
Identifiers
URN: urn:nbn:se:uu:diva-111427OAI: oai:DiVA.org:uu-111427DiVA: diva2:281153
Available from: 2009-12-14 Created: 2009-12-14 Last updated: 2011-01-11
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, Sanna

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