text: The evolution of interactome complexity is delineated in a study published in Nature. In this study it is first noted that the boundaries between prokaryotes, unicellular eukaryotes and multicellular eukaryotes are accompanied by orders-of-magnitude reductions in effective population size, with concurrent amplifications of the effects of random genetic drift. The resultant decline in the efficiency of selection seems to be sufficient to influence a wide range of attributes at the genomic level in a nonadaptive manner. The Nature study shows that the variation in the power of random genetic drift is also capable of influencing phylogenetic diversity at the subcellular and cellular levels. Thus, population size would have to be considered as a potential determinant of the mechanistic pathways underlying long-term phenotypic evolution. In the study it is further shown that a phylogenetically broad inverse relation exists between the power of drift and the structural integrity of protein subunits. Thus, the accumulation of mildly deleterious mutations in populations of small size induces secondary selection for protein–protein interactions that stabilize key gene functions, mitigating the structural degradation promoted by inefficient selection. By this means, the complex protein architectures and interactions essential to the genesis of phenotypic diversity may initially emerge by non-adaptive mechanisms.