There are various mechanisms through which protein domain or whole proteins may have been duplicated. On the largest scale, whole genome duplication such as those seen in the vertebrate genomes duplicated whole gene families, including postsynaptic proteins, hormone receptors and muscle proteins, and thereby dramatically increased the domain content and expanded networks [42, 63, 64] . On the other end of the scale, domains and proteins have been duplicated through genetic mechanisms like exon-shuffling, retrotranspositions, recombination and horizontal gene transfer [65] [66] [67] . Since the genetic forces, like exon-shuffling and genome duplication vary among species, the total number of domains and the types of domains present fluctuate per genome. Interestingly, comparative analyses of genomes have shown that the number of unique domains encoded in organisms is generally proportional to its genome size [60, 68] . Within genomes, the number of domains per gene, the socalled modularity, is related to genome size via a power-law, which is essentially the relation between the frequency f and an occurrence x raised by a scaling constant k (i.e., f (x) x k ) [69, 70] . A similar correlation is found when the multi-domain architecture is compared to the number of cell types that is present in an organism, i.e., the organism complexity or when the number of domains in a abundant superfamily is plotted against genome size (Fig. 2) [71, 72] .