Although sequence and phylogenetic analysis provide a relatively straightforward way for looking at domain divergence, comparison of solved protein structures has shown that protein tertiary organizations are much more conserved (>50%) than their primary sequence (>5%) [41] . For this reason, protein structures and their models provide significantly more insight into the relations of protein domains and how domain families diverged [16] . For example, the inactive guanylate kinase (GK) domain present in the MAGUK family was shown to originate from an active form of the GK domain residing in Ca2+ channel beta-subunits (CACNBs) through both sequence and structural comparison [42] . Furthermore, identification of functionally or structurally related amino acid sites in a fold sheds light on the complex, co-evolutionary dynamics that took place during selection [43] .