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

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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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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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Correspondence to Christopher G Knight.

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The authors declare no competing financial interests.

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) doi:10.1038/ng1867

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