A phylogenomic data-driven exploration of viral origins and evolution

Nasir, Arshan; Caetano-Anollés, Gustavo

One scheme for classifying protein domains based on their structural, functional, and evolutionary relationships is the Structural Classification of Proteins (SCOP) database (9) . SCOP is considered the "gold stan-dard" in the classification of protein domains with known 3D structures and provides useful evolutionary information on domains grouped into fold families (FFs) and fold superfamilies (FSFs). FFs include domains that are typically more than 30% identical in their sequence composition. In turn, FSFs group FFs with common 3D structural cores and biochemical properties, albeit with low sequence identity (could be <15%). Hence, FSFs are more conserved in evolution and suitable for deep evolutionary comparisons (5, 12) . This is demonstrated by the fact that nearly half a million protein sequences in UniProtKB/Swiss-Prot (13) map only to~2300 FSFs (SCOP 1.75). Empirically, it has been shown that protein structure is at least 3 to 10 times more conserved than sequence (14) . Moreover, the conserved 3D core of FSF domains rarely (that is, 0.4 to 4%) evolves by convergent evolution (15) . A focus on FSF domains also puts bounds on the molecular diversity of viruses and cellular organisms. This and other advantages (16) make FSF domains reliable phylogenetic characters for evolutionary studies, especially when the focus is to reconstruct the deep evolutionary history of life [as shown previously (5, (17) (18) (19) ].