Presser Aviva, Elowitz Michael B, Kellis Manolis, Kishony Roy
School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):950-4. doi: 10.1073/pnas.0707293105. Epub 2008 Jan 16.
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.
基因复制是蛋白质相互作用网络进化中的一种重要机制。复制之后会发生相互作用的增减，以某种未知速率重塑网络。由于重塑可能会改变复制后的相互作用集中网络基序的分布，因此应该可以通过追踪这些基序的进化来研究网络重塑。我们开发了一个数学框架，结合来自比较基因组学和蛋白质组学研究的复制数据，使我们能够推断复制前网络的连通性以及连通性随时间的变化。我们聚焦于酿酒酵母中的全基因组复制（WGD）事件。该模型使我们能够预测WGD之前基因间相互作用的频率以及复制后相互作用增加和减少的概率。我们发现，复制前网络中预测的自相互作用频率显著高于当今网络中观察到的频率。这可能表明现代网络与祖先网络之间存在结构差异、同源基因之间相互作用的优先添加或保留，或者存在保留自相互作用蛋白副本的选择压力。
