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Proc Natl Acad Sci U S A. 2008 Jan 29;105(4):1243-8. doi: 10.1073/pnas.0711043105. Epub 2008 Jan 23.

Preferential protection of protein interaction network hubs in yeast: evolved functionality of genetic redundancy.

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Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.


The widely observed dispensability of duplicate genes is typically interpreted to suggest that a proportion of the duplicate pairs are at least partially redundant in their functions, thus allowing for compensatory affects. However, because redundancy is expected to be evolutionarily short lived, there is currently debate on both the proportion of redundant duplicates and their functional importance. Here, we examined these compensatory interactions by relying on a genome wide data analysis, followed by experiments and literature mining in yeast. Our data, thus, strongly suggest that compensated duplicates are not randomly distributed within the protein interaction network but are rather strategically allocated to the most highly connected proteins. This design is appealing because it suggests that many of the potentially vulnerable nodes that would otherwise be highly sensitive to mutations are often protected by redundancy. Furthermore, divergence analyses show that this association between redundancy and protein connectivity becomes even more significant among the ancient duplicates, suggesting that these functional overlaps have undergone purifying selection. Our results suggest an intriguing conclusion-although redundancy is typically transient on evolutionary time scales, it tends to be preserved among some of the central proteins in the cellular interaction network.

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