Non-adaptive origins of interactome complexity

  • An Addendum to this article was published on 26 November 2014


The boundaries between prokaryotes, unicellular eukaryotes and multicellular eukaryotes are accompanied by orders-of-magnitude reductions in effective population size, with concurrent amplifications of the effects of random genetic drift and mutation1. The resultant decline in the efficiency of selection seems to be sufficient to influence a wide range of attributes at the genomic level in a non-adaptive manner2. A key remaining question concerns the extent to which variation in the power of random genetic drift is capable of influencing phylogenetic diversity at the subcellular and cellular levels2,3,4. Should this be the case, population size would have to be considered as a potential determinant of the mechanistic pathways underlying long-term phenotypic evolution. Here we demonstrate a phylogenetically broad inverse relation between the power of drift and the structural integrity of protein subunits. This leads to the hypothesis that the accumulation of mildly deleterious mutations in populations of small size induces secondary selection for protein–protein interactions that stabilize key gene functions. By this means, the complex protein architectures and interactions essential to the genesis of phenotypic diversity may initially emerge by non-adaptive mechanisms.

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Figure 1: Structural deficiencies in soluble proteins promote protein associations.
Figure 2: Structural degradation enhances PWIT and promotes protein interactivity in species with small population sizes.


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A.F. was supported by National Institutes of Health grant R01GM072614, and by the Institute of Biophysical Dynamics and the Department of Computer Science at The University of Chicago. M.L. was supported by National Institutes of Health grant R01GM036827 and National Science Foundation grant EF-0827411.

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A.F. and M.L. conceived the project and wrote the paper. A.F. collected the orthologue groups across 36 species with sufficient structural representation, performed the structural analysis and determined the interaction propensities across orthologues.

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Correspondence to Ariel Fernández or Michael Lynch.

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The authors declare no competing financial interests.

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The file contains Supplementary Information Parts 1 and 2, which include Supplementary Text and Data, Supplementary Tables 1-7, Supplementary Figures 1-7 with legends and additional references. (PDF 1858 kb)

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Fernández, A., Lynch, M. Non-adaptive origins of interactome complexity. Nature 474, 502–505 (2011).

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