Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Selection-driven genome reduction in bacteria
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
2012 (English)In: PLOS genetics, ISSN 1553-7404, Vol. 8, no 6, e1002787- p.Article in journal (Refereed) Published
Abstract [en]

Gene loss by deletion is a common evolutionary process in bacteria, as exemplified by bacteria with small genomes that have evolved from bacteria with larger genomes by reductive processes. The driving force(s) for genome reduction remains unclear, and here we examined the hypothesis that gene loss is selected because carriage of superfluous genes confers a fitness cost to the bacterium. In the bacterium Salmonella enterica, we measured deletion rates at 11 chromosomal positions and the fitness effects of several spontaneous deletions. Deletion rates varied over 200-fold between different regions with the replication terminus region showing the highest rates. Approximately 25% of the examined deletions caused an increase in fitness under one or several growth conditions, and after serial passage of wild-type bacteria in rich medium for 1,000 generations we observed fixation of deletions that substantially increased bacterial fitness when reconstructed in a non-evolved bacterium. These results suggest that selection could be a significant driver of gene loss and reductive genome evolution.

Place, publisher, year, edition, pages
2012. Vol. 8, no 6, e1002787- p.
Keyword [en]
selection, genome reduction, bacteria
National Category
Genetics
Research subject
Biology with specialization in Microbiology
Identifiers
URN: urn:nbn:se:uu:diva-172783DOI: 10.1371/journal.pgen.1002787ISI: 000305961000046OAI: oai:DiVA.org:uu-172783DiVA: diva2:515763
Available from: 2012-04-15 Created: 2012-04-15 Last updated: 2012-08-01Bibliographically approved
In thesis
1. Dynamics and Mechanisms of Adaptive Evolution in Bacteria
Open this publication in new window or tab >>Dynamics and Mechanisms of Adaptive Evolution in Bacteria
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Determining the properties of mutations is fundamental to understanding the mechanisms of adaptive evolution. The major goal of this thesis is to investigate the mechanisms of bacterial adaptation to new environments using experimental evolution. Different types of mutations were under investigations with a particular focus on genome rearrangements. Adaptive evolution experiments were focused on the development of bacterial resistance to antibiotics.

In paper I, we performed stochastic simulations to examine the role of gene amplification in promoting the establishment of new gene functions. The results show that gene amplification can contribute to creation of new gene functions in nature. In paper II, the evolution of β-lactam resistance was studied by evolving S. typhimurium carrying a β-lactamase gene towards increased resistance against cephalosporins. Our results suggest that gene amplification is likely to provide an immediate solution at the early stage of adaptive evolution and subsequently facilitate further stable adaptation. In paper III, we isolated spontaneous deletion mutants with increased competitive fitness, which indicated that genome reduction could be driven by selection. To test this hypothesis, independent lineages of wild type S. typhimurium were serially passaged for 1000 generations and we observed fixation of deletions that significantly increased bacterial fitness when reconstructed in wild type genetic background. In paper IV, we developed a new strategy combining 454 pyrosequencing technology and a ‘split mapping’ computational method to identify unique junction sequences formed by spontaneous genome rearrangements. A high steady-state frequency of rearrangements in unselected bacterial populations was suggested from our results. In paper V, the rates, mechanisms and fitness effects of colistin resistance in S. typhimurium were determined. The high mutation rate and low fitness costs suggest that colistin resistance could develop in clinical settings. In paper VI, a novel Metallo-β-lactamase (MBL) with low resistance against β-lactam antibiotics was employed as the ancestral protein in a directed evolution experiment to examine how an enzyme evolves towards increased resistance. For most isolated mutants, in spite of their significantly increased resistance, both mRNA and protein levels were decreased as compared with the parental protein, suggesting that the catalytic activity had increased.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 64 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 770
Keyword
adaptive evolution, mutation, genome rearrangements, antibiotic resistance, gene amplification, genome reduction, directed evolution
National Category
Microbiology
Research subject
Biology with specialization in Microbiology
Identifiers
urn:nbn:se:uu:diva-172786 (URN)978-91-554-8354-8 (ISBN)
Public defence
2012-06-05, C10:305, BMC, Husargatan 3, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2012-05-14 Created: 2012-04-15 Last updated: 2012-08-01Bibliographically approved

Open Access in DiVA

fulltext(315 kB)253 downloads
File information
File name FULLTEXT01.pdfFile size 315 kBChecksum SHA-512
9b48dd5054c92e92d1783e7980cc12663d334e960dd60f6ad76af2aa3f352dcc4f5ad1cf8cddb8b557cf413919a1f4ac71b458d30fc162c95514f072c1e62403
Type fulltextMimetype application/pdf

Other links

Publisher's full text

Search in DiVA

By author/editor
Sun, SongBerg, OttoAndersson, Dan I.
By organisation
Department of Medical Biochemistry and MicrobiologyComputational and Systems Biology
Genetics

Search outside of DiVA

GoogleGoogle Scholar
Total: 253 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 829 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf