Abstract
According to what we term the balance hypothesis, an imbalance in the concentration of the subcomponents of a protein–protein complex can be deleterious1. If so, there are two consequences: first, both underexpression and overexpression of protein complex subunits should lower fitness, and second, the accuracy of transcriptional co-regulation of subunits should reflect the deleterious consequences of imbalance. Here we show that all these predictions are upheld in yeast (Saccharomyces cerevisiae). This supports the hypothesis2,3 that dominance is a by-product of physiology and metabolism rather than the result of selection to mask the deleterious effects of mutations. Beyond this, single-gene duplication of protein subunits is expected to be harmful, as this, too, leads to imbalance. As then expected, we find that members of large gene families are rarely involved in complexes. The balance hypothesis therefore provides a single theoretical framework for understanding components both of dominance and of gene family size.
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Acknowledgements
We thank C. Scharfe, L. Steinmetz, D. Bray and B. Charlesworth for comments on the manuscript. B.P. is supported by an EU Marie Curie Fellowship, C.P. by a Royal Society/Nato Fellowship and L.D.H. by the BBSRC.
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Papp, B., Pál, C. & Hurst, L. Dosage sensitivity and the evolution of gene families in yeast. Nature 424, 194–197 (2003). https://doi.org/10.1038/nature01771
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DOI: https://doi.org/10.1038/nature01771
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