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Variation in mutational robustness between different proteins and the predictability of fitness effects
Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. (Peter Lind)ORCID iD: 0000-0003-1510-8324
2017 (English)In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 34, no 2, 408-418 p.Article in journal (Refereed) Published
Abstract [en]

Random mutations in genes from disparate protein classes may have different distributions of fitness effects (DFEs) depending on different structural, functional and evolutionary constraints. We measured the fitness effects of 156 single mutations in the genes encoding AraC (transcription factor), AraD (enzyme), and AraE (transporter) used for bacterial growth on L- arabinose. Despite their different molecular functions these genes all had bimodal DFEs with most mutations either being neutral or strongly deleterious, providing a general expectation for the DFE. This contrasts with the unimodal DFEs previously obtained for ribosomal protein genes where most mutations were slightly deleterious. Based on theoretical considerations, we suggest that the 33-fold higher average mutational robustness of ribosomal proteins is due to stronger selection for reduced costs of translational and transcriptional errors. While the large majority of synonymous mutations were deleterious for ribosomal proteins genes, no fitness effects could be detected for the AraCDE genes. Four mutations in AraC and AraE increased fitness, suggesting that slightly advantageous mutations make up a significant fraction of the DFE, but that they often escape detection due to the limited sensitivity of commonly used fitness assays. We show that the fitness effects of amino acid substitutions can be predicted based on evolutionary conservation, but that weakly deleterious mutations are less reliably detected. This suggests that large-effect mutations and the fraction of highly deleterious mutations can be computationally predicted, but that experiments are required to characterize the DFE close to neutrality, where many mutations ultimately fixed in a population will occur.

Place, publisher, year, edition, pages
2017. Vol. 34, no 2, 408-418 p.
Keyword [en]
mutation, fitness, protein, robustness, arabinose operon, bacteria
National Category
Evolutionary Biology Genetics Microbiology
Research subject
Genetics; Microbiology; evolutionär genetik
Identifiers
URN: urn:nbn:se:umu:diva-128803DOI: 10.1093/molbev/msw239ISI: 000396511300010PubMedID: 28025272OAI: oai:DiVA.org:umu-128803DiVA: diva2:1056494
Funder
Swedish Research Council
Available from: 2016-12-14 Created: 2016-12-14 Last updated: 2017-04-21Bibliographically approved

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Lind, Peter A.
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CiteExportLink to record
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Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
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  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
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  • asciidoc
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