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Mutational robustness of ribosomal protein genes
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. (Dan I Andersson)
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Molecular Evolution.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
2010 (English)In: Science, ISSN 0036-8075, Vol. 330, no 6005, 825-827 p.Article in journal (Refereed) Published
Abstract [en]

The distribution of fitness effects (DFE) of mutations is of fundamental importance for understanding evolutionary dynamics and complex diseases and for conserving threatened species. DFEs estimated from DNA sequences have rarely been subject to direct experimental tests. We used a bacterial system in which the fitness effects of a large number of defined single mutations in two ribosomal proteins were measured with high sensitivity. The obtained DFE appears to be unimodal, where most mutations (120 out of 126) are weakly deleterious and the remaining ones are potentially neutral. The DFEs for synonymous and nonsynonymous substitutions are similar, suggesting that in some genes, strong fitness constraints are present at the level of the messenger RNA.

Place, publisher, year, edition, pages
2010. Vol. 330, no 6005, 825-827 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-132260DOI: 10.1126/science.1194617ISI: 000283855700044PubMedID: 21051637OAI: oai:DiVA.org:uu-132260DiVA: diva2:357343
Available from: 2010-10-18 Created: 2010-10-18 Last updated: 2011-06-29Bibliographically approved
In thesis
1. Evolutionary Dynamics of Mutation and Gene Transfer in Bacteria
Open this publication in new window or tab >>Evolutionary Dynamics of Mutation and Gene Transfer in Bacteria
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The study of bacterial evolution is fundamental for addressing current problems of antibiotic resistance and emerging infectious diseases and lays a solid foundation for successful and rational design in biotechnology and synthetic biology. The main aim of this thesis is to test evolutionary hypotheses, largely based on theoretical considerations and sequence analysis, by designing scenarios in a laboratory setting to obtain experimental data. Paper I examines how genomic GC-content can be reduced following a change in mutation rate and spectrum. Transcription-related biases in mutation location were found, but no replicative bias was detected. Paper II explores the distribution of fitness effects of random substitutions in two ribosomal protein genes using a highly sensitive fitness assay. The substitutions had a weakly deleterious effect, with low frequencies of both neutral and inactivating mutations. The surprising finding that synonymous and non-synonymous substitutions have very similar distribution of fitness effects suggests that, at least for these genes, fitness constraints are present mainly on the level of mRNA instead of protein. Paper III examines selective barriers to inter-species gene transfer by constructing mutants with a native gene replaced by an orthologue from another species. Results suggest that the fitness costs of these gene replacements are large enough to provide a barrier to this kind of horizontal gene transfer in nature. The paper also examines possible compensatory mechanisms that can reduce the cost of the poorly functioning alien genes and found that gene amplification acts as a first step to improve the selective contribution after transfer. Paper IV investigates the fitness constraints on horizontal gene transfer by inserting DNA from other species into the Salmonella chromosome. Results suggest that insertion of foreign DNA often is neutral and the manuscript provides new experimental data for theoretical analysis of interspecies genome variation and horizontal gene transfer between species.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 80 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 611
fitness cost, bacterial evolution, gene amplification, mutational biases, GC content, synonymous substitutions, horizontal gene transfer, experimental evolution
National Category
Microbiology in the medical area Microbiology Genetics Biological Sciences
Research subject
urn:nbn:se:uu:diva-132262 (URN)978-91-554-7923-7 (ISBN)
Public defence
2010-12-03, C4:301, BMC, Husargatan 3, Uppsala, 13:00 (English)
Available from: 2010-11-11 Created: 2010-10-18 Last updated: 2011-01-13Bibliographically approved

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