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Genetic adaptation to growth under laboratory conditions in Escherichia coli and Salmonella enterica
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.ORCID iD: 0000-0002-8218-3263
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.
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2018 (English)In: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 9, article id 756Article in journal (Refereed) Published
Abstract [en]

Experimental evolution under controlled laboratory conditions is becoming increasingly important to address various evolutionary questions, including, for example, the dynamics and mechanisms of genetic adaptation to different growth and stress conditions. In such experiments, mutations typically appear that increase the fitness under the conditions tested (medium adaptation), but that are not necessarily of interest for the specific research question. Here, we have identified mutations that appeared during serial passage of E. coli and S. enterica in four different and commonly used laboratory media and measured the relative competitive fitness and maximum growth rate of 111 genetically re-constituted strains, carrying different single and multiple mutations. Little overlap was found between the mutations that were selected in the two species and the different media, implying that adaptation occurs via different genetic pathways. Furthermore, we show that commonly occurring adaptive mutations can generate undesired genetic variation in a population and reduce the accuracy of competition experiments. However, by introducing media adaptation mutations with large effects into the parental strain that was used for the evolution experiment, the variation (standard deviation) was decreased 10-fold, and it was possible to measure fitness differences between two competitors as small as |s| < 0.001.

Place, publisher, year, edition, pages
2018. Vol. 9, article id 756
National Category
Evolutionary Biology Microbiology
Research subject
Biology with specialization in Evolutionary Organismal Biology; Biology with specialization in Microbiology
Identifiers
URN: urn:nbn:se:uu:diva-347617DOI: 10.3389/fmicb.2018.00756ISI: 000430941800001PubMedID: 29755424OAI: oai:DiVA.org:uu-347617DiVA, id: diva2:1195397
Funder
Swedish Research Council, 2016-03383Swedish Research Council, 2014-4479
Note

Michael Knopp, Lisa M. Albrecht, Erik Lundin and Ulrika Lustig contributed equally to this work.

Available from: 2018-04-05 Created: 2018-04-05 Last updated: 2018-10-02Bibliographically approved
In thesis
1. Evolution of New Genes and Functions
Open this publication in new window or tab >>Evolution of New Genes and Functions
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

To answer major evolutionary questions, we need a better understanding of the effects of mutations on specific functions and organism fitness. The aim of this thesis was to elucidate how new functions evolve and potential trade-offs with the original function.

Paper I identified a bimodal distribution of fitness effects of mutations in Salmonella enterica HisA protein. Most mutations negatively affected protein function but the effect was masked at high gene expression. Expression levels and the extent to which the studied protein limited growth were important in determining the fitness effects of mutations. No fitness prediction tool was satisfactorily alone but in combination predictions were improved.

In Paper II, S. enterica HisA was evolved to acquire TrpF activity. Numerous pathways towards improved TrpF activity were examined and several improvement mechanisms were identified. Improved TrpF activity extensively reduced the original activity, generalist enzymes were rare and restoring original activity after an initial loss was difficult. Furthermore, expression levels had a major impact on the shape of the trade-off curve.

In Paper III, adaptation during serial passage of Escherichia coli and S. enterica under laboratory conditions were examined. Adaptive mutations were identified in four different laboratory media and their fitness effects were determined. Little overlap in mutation spectra was found in the different media and species suggesting that adaptation was media-specific. Furthermore, media adaptation mutations reduced the accuracy of fitness assays and the use of pre-adapted strains improved the sensitivity of fitness assays 10-fold.

Paper IV examined evolution of novel metabolic capabilities in S. enterica by analyzing growth on 124 non-native carbon sources. Growth was observed on 25 compounds and for five of these, the causative mutation was identified. Increased gene expression of cryptic genes was a major mechanism for acquiring the novel phenotypes.

In conclusion, my results show that in most cases many types of mutations can improve a function and allow adaptive evolution but this often is associated with a trade-off and loss in other abilities. Increased gene expression was a major mechanism by which bacteria could compensate for loss of an activity as well as acquire new metabolic capabilities.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. p. 72
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1502
National Category
Microbiology
Research subject
Biology with specialization in Microbiology
Identifiers
urn:nbn:se:uu:diva-362157 (URN)978-91-513-0463-2 (ISBN)
Public defence
2018-11-23, B42, BMC, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2018-10-31 Created: 2018-10-02 Last updated: 2018-10-31

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Knöppel, AnnaKnopp, MichaelAlbrecht, Lisa MLundin, ErikLustig, UlrikaNäsvall, JoakimAndersson, Dan I

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