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MBE Advance Access originally published online on May 23, 2008
Molecular Biology and Evolution 2008 25(8):1530-1533; doi:10.1093/molbev/msn122
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© The Author 2008. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Letters

Natural Selection against Protein Aggregation on Self-Interacting and Essential Proteins in Yeast, Fly, and Worm

Yiwen Chen*,{dagger},1 and Nikolay V. Dokholyan*,{ddagger}

* Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill
{dagger} Department of Physics and Astronomy, University of North Carolina at Chapel Hill
{ddagger} Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill

E-mail: dokh{at}med.unc.edu.

Accepted for publication May 19, 2008.

Protein aggregation is the phenomenon of protein self-association potentially leading to detrimental effects on physiology, which is closely related to numerous human diseases such as Alzheimer's and Parkinson's disease. Despite progress in understanding the mechanism of protein aggregation, how natural selection against protein aggregation acts on subunits of protein complexes and on proteins with different contributions to organism fitness remains largely unknown. Here, we perform a proteome-wide analysis by using an experimentally validated algorithm TANGO and utilizing sequence, interactomic and phenotype-based functional genomic data from yeast, fly, and nematode. We find that proteins that are capable of forming homooligomeric complex have lower aggregation propensity compared with proteins that do not function as homooligomer. Further, proteins that are essential to the fitness of an organism have lower aggregation propensity compared with nonessential ones. Our finding suggests that the selection force against protein aggregation acts across different hierarchies of biological system.

Key Words: natural selection • protein aggregation • functional genomics • proteome • Drosophila melanogaster • Caenorhabditis elegans

1 Present address: Department of Genetics, Harvard Medical School, Boston, MA

Michele Vendruscolo, Associate Editor


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