A phylogenomic data-driven exploration of viral origins and evolution

Nasir, Arshan; Caetano-Anollés, Gustavo

Here, we analyzed a total of 5080 completely sequenced proteomes from cells and viruses and assigned FSF domains to their proteins using structure-based hidden Markov models (HMMs) defined by the SUPER-FAMILY database (version 1.75) (20) . The viral data set included 3460 proteomes from 1649 double-stranded DNA (dsDNA), 534 singlestranded DNA (ssDNA), 166 double-stranded RNA (dsRNA), 991 single-stranded RNA (ssRNA) (881 plus sense and 110 minus sense), and 120 retrotranscribing (56 ssRNA-RT and 64 dsDNA-RT) viruses (table S1), whereas the cellular data set included 1620 proteomes from 122, 1115, and 383 organisms from the superkingdoms Archaea, Bacteria, and Eukarya, respectively (table S2) . Applying both comparative genomic and phylogenomic strategies, we asked a number of crucial questions: Can we quantify viral diversity? How many unique protein folds exist in the virosphere? What is the predominant direction of gene transfer (cell-to-virus or virus-to-cell)? Are viruses infecting different organisms evolutionarily related? Can we identify protein folds that define viral lineages based on common virion architectures? Are viruses monophyletic or polyphyletic? Where do viruses lie on the tree of life? What were the earliest replicons?