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Published January 22, 2008 | Published + Supplemental Material
Journal Article Open

The evolutionary dynamics of the Saccharomyces cerevisiae protein interaction network after duplication


Gene duplication is an important mechanism in the evolution of protein interaction networks. Duplications are followed by the gain and loss of interactions, rewiring the network at some unknown rate. Because rewiring is likely to change the distribution of network motifs within the duplicated interaction set, it should be possible to study network rewiring by tracking the evolution of these motifs. We have developed a mathematical framework that, together with duplication data from comparative genomic and proteomic studies, allows us to infer the connectivity of the preduplication network and the changes in connectivity over time. We focused on the whole-genome duplication (WGD) event in Saccharomyces cerevisiae. The model allowed us to predict the frequency of intergene interaction before WGD and the post duplication probabilities of interaction gain and loss. We find that the predicted frequency of self-interactions in the preduplication network is significantly higher than that observed in today's network. This could suggest a structural difference between the modern and ancestral networks, preferential addition or retention of interactions between ohnologs, or selective pressure to preserve duplicates of self-interacting proteins.

Additional Information

© 2008 by the National Academy of Sciences. Edited by Leonid Kruglyak, Princeton University, Princeton, NJ, and accepted by the Editorial Board November 20, 2007 (received for review August 2, 2007). Published online before print January 16, 2008, doi: 10.1073/pnas.0707293105. This article is a PNAS Direct Submission. L.K. is a guest editor invited by the Editorial Board. We acknowledge N. Barkai, M. Brenner, A. DeLuna, E. Lieberman, I. Nachman, I. Wapinski, and K. Wolfe for their advice and helpful discussions and E. Lieberman and R. Milo for critical readings of the manuscript. This work was supported in part by National Institutes of Health Grants GM068763 (to M.B.E.) and R01GM081617 (to R.K.). A.P. was supported by a National Science Foundation Graduate Fellowship and a National Defense Science and Engineering Graduate Fellowship. Author contributions: A.P., M.B.E., and R.K. designed research; A.P. performed research; A.P., M.K., and R.K. analyzed data; and A.P., M.B.E., M.K., and R.K. wrote the paper. The authors declare no conflict of interest. This article contains supporting information online at www.pnas.org/cgi/content/full/0707293105/DC1.

Attached Files

Published - PREpnas08.pdf

Supplemental Material - 07293Fig4.pdf

Supplemental Material - 07293Fig5.pdf

Supplemental Material - 07293SuppText.pdf

Supplemental Material - 07293Table3.pdf

Supplemental Material - 07293Table4.pdf


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August 22, 2023
October 17, 2023