We carried out an extensive comparative analysis of theoretical interactomes for 146 complete genomes (archaea: 15, bacteria: 122, and eukarya: 9) using a protein structural interactome map method under a homogeneous paradigm: protein family-family interaction networks (an interactome is a set of all protein family interactions within a proteome). All the interactomes were scale-free networks, and the number of interaction pairs increased linearly along with the number of protein families. We found a fundamental difference among prokaryotic and eukaryotic interactomes: eukarya had many more hub families than archaea and bacteria, and certain special hub families characteristically determined the shape of the eukaryotic interactomes. Our finding suggests that a very small number of expansive protein families led the growth of interactomes and seemed to have played a key role in species diversification.