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Evolution of new gene functions: simulation and analysis of the amplification model.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Molecular Evolution.
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 Evolution, Genomics and Systematics, Molecular Evolution.
2009 (English)In: Genetica, ISSN 0016-6707, E-ISSN 1573-6857, Vol. 135, no 3, 309-324 p.Article in journal (Refereed) Published
Abstract [en]

Creation of new genes and functions is a central feature of evolution. Duplication of existing genes has long been assumed to be the source of new genes, but the precise mechanism has remained unclear. One suggestion is that new genes are created via temporary amplifications, which simultaneously increase both the selective advantage of weak, pre-existing secondary functions and the target for optimizing mutations. This paper examines the amplification model by formalizing it into a mathematical framework. This framework is used to perform stochastic (Monte Carlo) simulations. In addition, experimental data from Salmonella typhimurium LT2 are used to support the modelling, by providing estimates for parameter values. The results show that amplification of tandem repeats is likely to contribute to creation of new genes in nature.

Place, publisher, year, edition, pages
2009. Vol. 135, no 3, 309-324 p.
Keyword [en]
Gene amplification, gene innovation, population dynamics, stochastic modelling
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:uu:diva-98894DOI: 10.1007/s10709-008-9289-zISI: 000263833900007PubMedID: 18568430OAI: oai:DiVA.org:uu-98894DiVA: diva2:201491
Available from: 2009-03-04 Created: 2009-03-04 Last updated: 2017-12-13Bibliographically 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

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Andersson, Dan I.Berg, Otto G

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