Background: 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. 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. Results. In 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. Conclusions. These 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.
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