Given the amount of domain duplication and apparent selection for specific multi-domain encoding genes in, for example, vertebrates, it may come as little surprise that not all domains have had the same tendency to recombine and distribute themselves over the genomes [68, 73] . In fact, some are highly abundant and can be found in many different multi-domain architectures, whereas others are abundant yet confined to a small sample of architectures or not abundant at all [68, 70] . Is there any significant correlation between the propensity to distribute and the functional roles domains have in cellular pathways? Some of the most abundant domains can be found in association with cellular signaling cascades and have been shown to accumulate non-linearly in relation to the overall number of domains encoded or the genome size [70] . Additionally, the on-set of the exponential expansion of the number of abundant and highly recombining domains has been linked to the appearance of multicellularity [70] . A reoccurring theme among these abundant domains is the function of protein-protein interaction and it appears that particularly these, usually globular domains, have been particularly selected for in more complex organisms [70] . This positive relation is underlined by the association of these abundant domains with disease such as cancer and gene essentiality as the highly interacting proteins that they are part of have central places in cascades and need to orchestrate a high number of molecular connections [74, 75] . Their shape and coding regions, which usually lie within the boundaries of one or two exons, make them ideally suited for such a selection, since domains are most frequently gained through insertions at the N-or C-terminus and through exon shuffling [76] [77] [78] .