Nonadaptive origins of interactome complexity

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 and mutation1. The resultant decline in the efficiency of selection appears to be sufficient to influence a wide range of attributes at the genomic level in a nonadaptive manner2. A key remaining question concerns the extent to which variation in the power of random genetic drift is capable of influencing phylogenetic diversity at the subcellular and cellular levels2–4. Should this be the case, population size would have to be considered as a potential determinant of the mechanistic pathways underlying long-term phenotypic evolution. Here we demonstrate a phylogenetically broad inverse relationship between the power of drift and the structural integrity of protein subunits. This leads to the hypothesis that the accumulation of mildly deleterious mutations in populations of small size induces secondary selection for protein-protein interactions that stabilize key gene functions. By this means, the complex protein architectures and interactions essential to the genesis of phenotypic diversity may initially emerge by nonadaptive mechanisms.