Several observations could be extracted for the PAAD domain: (i) Based on a multiple sequence alignment (MSA) of the PAAD domain sequences it is evident that the 5 viral proteins were diverged significantly ( Figure 4B ). All 5 viral proteins reside in one cluster, in the phylogenetic tree, together with other mammals as their sibling in the tree ( Figure 4A, blue font) . The domain architecture within the protein of the family is best explained by an initial extensive duplication of the PAAD domain ( Figure 4A Figure 4A , red font). Note that these proteins spread throughout the sequence-based tree. Presumably, it is a reflection of a domain loss event. Some of these proteins are fragments (e.g., Q5T3V8_HUMAN), and others include less characterized PfamB domains [32] (e.g., IFI4L_MOUSE, Q3UPZ5_MOUSE).