Abstract
BackgroundA protein-protein interaction network (PIN) was suggested to be a disassortative network, in which interactions between high- and low-degree nodes are favored while hub-hub interactions are suppressed. It was postulated that a disassortative structure minimizes unfavorable cross-talks between different hub-centric functional modules and was positively selected in evolution. However, by re-examining yeast PIN data, several researchers reported that the disassortative structure observed in a PIN might be an experimental artifact. Therefore, the existence of a disassortative structure and its possible evolutionary mechanism remains unclear.ResultsIn this study, we investigated PINs from the yeast, worm, fly, human, and malaria parasite including four different yeast PIN datasets. The analyses showed that the yeast, worm, fly, and human PINs are disassortative while the malaria parasite PIN is not. By conducting simulation studies on the basis of a duplication-divergence model, we demonstrated that a preferential duplication of low- and high-degree nodes can generate disassortative and non-disassortative networks, respectively. From this observation, we hypothesized that the difference in degree dependence on gene duplications accounts for the difference in assortativity of PINs among species. Comparison of 55 proteomes in eukaryotes revealed that genes with lower degrees showed higher gene duplicabilities in the yeast, worm, and fly, while high-degree genes tend to have high duplicabilities in the malaria parasite, supporting the above hypothesis.ConclusionsThese results suggest that disassortative structures observed in PINs are merely a byproduct of preferential duplications of low-degree genes, which might be caused by an organism's living environment.
Highlights
A protein-protein interaction network (PIN) was suggested to be a disassortative network, in which interactions between high- and low-degree nodes are favored while hub-hub interactions are suppressed
A new link is preferentially attached between two duplicated nodes to create a cross-interaction when they share many common neighbors. We showed that this model can the best reproduce structural features of the yeast PIN, including scale-freeness, a small number of cross-interactions, and a skewed distribution of triangles composed of three nodes and three links
We show that the yeast, worm, fly, and human PINs have disassortative structures, while malaria parasite PIN is not disassortative
Summary
A protein-protein interaction network (PIN) was suggested to be a disassortative network, in which interactions between high- and low-degree nodes are favored while hub-hub interactions are suppressed. The number of links connected to a node is called a degree. A correlation between degrees of two nodes connected by a link is another feature characteristic of a network architecture. A network is called as assortative when r > 0, while it is disassortative when r < 0. Hubs are preferentially connected to other hubs, whereas in a disassortative network, hubs tend to attach to low-degree nodes. It was reported that social networks such as coauthorships of scientific papers or film actor collaborations are assortative, whereas technological and biological networks including Internet, food web, neural network, and PIN are disassortative [16]
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