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Unraveling adaptive evolution: how a single point mutation affects the protein coregulation network

Nature Genetics volume 38, pages 1015–1022 (2006)Cite this article

Abstract

Understanding the mechanisms of evolution requires identification of the molecular basis of the multiple (pleiotropic) effects of specific adaptive mutations. We have characterized the pleiotropic effects on protein levels of an adaptive single–base pair substitution in the coding sequence of a signaling pathway gene in the bacterium Pseudomonas fluorescens SBW25. We find 52 proteomic changes, corresponding to 46 identified proteins. None of these proteins is required for the adaptive phenotype. Instead, many are found within specific metabolic pathways associated with fitness-reducing (that is, antagonistic) effects of the mutation. The affected proteins fall within a single coregulatory network. The mutation 'rewires' this network by drawing particular proteins into tighter coregulating relationships. Although these changes are specific to the mutation studied, the quantitatively altered proteins are also affected in a coordinated way in other examples of evolution to the same niche.

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Figure 1: Typical and atypical examples of protein spots differing significantly in level between SM (ancestral) and LSWS (evolved) genotypes.
Figure 2: Trees of spot correlations among replicates.
Figure 3: Change in skew of correlation distribution between evolved and ancestral strains.
Figure 4: Minimal spanning tree for correlations among independently evolved WS (mat-forming) strains.

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Acknowledgements

We thank M. Fricker, O. Suleman and D. Bebber for ideas and assistance with network analyses; C. Maclean for discussions of the WS system; A. Spiers for assistance with P. fluorescens; S. Knight for assistance with the manuscript and the Natural Environment Research Council's Environmental Genomics program for funding.

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Author notes

  1. Christopher G Knight

    Present address: Manchester Interdisciplinary Biocentre, University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK

  2. Sripadi Prabhakar

    Present address: National Centre for Mass Spectrometry, Indian Institute of Chemical Technology, Hyderabad, 500 007, India

Authors and Affiliations

  1. Department of Plant Sciences, South Parks Road, Oxford, OX1 3RB, UK

    Christopher G Knight & Paul B Rainey

  2. Department of Biochemistry, Glycobiology Institute, South Parks Road, Oxford, OX1 3QU, UK

    Christopher G Knight, Nicole Zitzmann, Sripadi Prabhakar, Robin Antrobus, Raymond Dwek & Holger Hebestreit

  3. School of Biological Sciences, University of Auckland, P.O. Box 92019, Auckland, New Zealand

    Paul B Rainey

  4. Manchester Interdisciplinary Biocentre, University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK

    Sripadi Prabhakar

  5. National Centre for Mass Spectrometry, Indian Institute of Chemical Technology, Hyderabad, 500 007, India

    Christopher G Knight

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Supplementary information

Supplementary Fig. 1

Proteomic and Biolog data in relation to degradation pathways into the TCA cycle. (PDF 305 kb)

Supplementary Fig. 2

Protein levels across strains. (PDF 345 kb)

Supplementary Table 1

Proteins corresponding to spots found to differ significantly in expression between ancestral (SM) and evolved (LSWS) genotypes. (PDF 366 kb)

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Knight, C., Zitzmann, N., Prabhakar, S. et al. Unraveling adaptive evolution: how a single point mutation affects the protein coregulation network. Nat Genet 38, 1015–1022 (2006). https://doi.org/10.1038/ng1867

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