In order to justify the directionality of sequences from the hosts to the virus, we constructed for each of the 667 Pfam families a sequence-based tree (MSA based on the domain and not the full length sequence). We considered Pfam families in which only 1-2 viral proteins are included in the family, and families in which the percentage of the virus proteins in the family is small (,5%, Figure 3A ). The vast majority (547 families, 82%) of the analyzed Pfam families fulfilled these criteria ( Figure 3A , blue). We also requested that the viral proteins are clustered in sub-trees within the family tree. We counted the number of viral proteins spreading within the sequence alignment tree. We suggest that viral proteins that are clustered in a defined sub-tree (called Viral Cluster, VC) are likely to represent a single episode of acquired sequence from the host. Consequently, only a limited diversity among the closely related viruses is expected in view of the rest of the tree. 64% of the 547 Pfam families from the previous selection fulfill the requirement for clustered viral proteins. These are the Pfam families that contain #2 viral clusters (60%), and other families (4%) that are specified by a high degree of condensation (i.e. the ratio of the viral proteins to the number of VCs is $3). These filtration steps further reduced the list of relevant Pfam families to 335 ( Figure 3B ).