A phylogenomic data-driven exploration of viral origins and evolution

Nasir, Arshan; Caetano-Anollés, Gustavo

The origin and evolution of viruses remain difficult to explain. This stems from numerous philosophical and technical issues, including an experimental focus on single genes and consequent failure to take into account the complete makeup of viral proteomes. Perhaps the most challenging problems plaguing the deep evolutionary studies of viruses are the fast evolution and high mutation rates of most viral genes [especially RNA viruses (1) ]. This makes it difficult to unify viral families especially using sequence-based phylogenetic analysis. For example, the latest (2014) report of the International Committee on the Taxonomy of Viruses (ICTV) recognizes 7 orders, 104 families, 23 subfamilies, 505 genera, and 3186 viral species (2) . Under this classification, viral families belonging to the same order have likely diverged from a common ancestral virus. However, only 26 viral families have been assigned to an order, and the evolutionary relationships of most of them remain unclear. The number of viral families without an order is expected to continuously increase, especially with the discovery of novel viruses from atypical environments, and because genes of many viral families do not exhibit significant sequence similarities (3) . In fact, homologous proteins often diverge beyond recognition at sequence level after a relatively long evolutionary time has passed (4) . In such cases, traditional sequencebased homology searches [for example, Basic Local Alignment Search Tool (BLAST)] and alignment software perform very poorly. However, the three-dimensional (3D) packing of amino acid side chains in cores of protein structural domains retains its arrangement over long evolutionary periods (5) . Because homologous proteins often maintain 3D folds and biochemical properties, they can still be recognized at the structure and function levels (6) (7) (8) (9) (10) (11) . However, given the massive genetic and phenotypic viral diversity, this task has remained a big challenge.