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Recent advances have provided a first experimental protein interaction map of the human malaria parasite  P. falciparum , which appears to be remotely related to interactomes of other eukaryotes. Here, we present a comparative topological analysis of this experimentally determined web with a network of conserved interactions between proteins in  S. cerevisiae, C. elegans  and  D. melanogaster  that have an ortholog in  Plasmodium . Focusing on experimental interactions, we find a significant presence of a “rich-club,” a topological characteristic that features an “oligarchy” of highly connected proteins being intertwined with one another. In complete contrast, the network of interologs and particularly the web of evolutionary-conserved interactions in  P. falciparum  lack this feature. This observation prompts the question of whether this result points to a topological signature of the parasite's biology, since experimentally obtained interactions widely cover parasite-specific functions. Significantly, hub proteins that appear in such an oligarchy revolve around invasion functions, shaping an island of parasite-specific activities in a sea of evolutionary inherited interactions. This presence of a biologically unprecedented network feature in the human malaria parasite might be an artifact of the quality and the methods to obtain interaction data in this organism. Yet, the observation that rich-club proteins have distinctive and statistically significant functions that revolve around parasite-specific activities point to a topological signature of a parasitic life style.

Rich-Club Phenomenon in the Interactome of P. falciparum—Artifact or Signature of a Parasitic Life Style?