A phylogenomic data-driven exploration of viral origins and evolution

Nasir, Arshan; Caetano-Anollés, Gustavo

To confirm whether capsid/coat-related FSFs were indeed exclusive to viruses, we checked for the presence of 22 capsid/coat-related viral FSFs in the 1620 cellular proteomes that were sampled. Of the total 22 FSFs, 19 were either completely or nearly completely absent in cells (Table 3 ). Only the "Major capsid protein gp5" FSF (d.183.1) of Caudovirales (HK97-like lineage) was present in~24% of cellular proteomes. The HK97-like fold has been detected in the shell-forming protein (encapsulin) of some archaeal protein nanocompartments that store metabolic enzymes (48) . These nanocompartments are polyhedral protein shells that are morphologically similar to icosahedral viruses. Because archaeal and bacterial encapsulins are homologous, it is likely that prokaryotic microcompartments are closely related to ancient viral capsids (49) . Those of bacterial carboxysomes are also morphologically similar to viral capsids (50) but are built from protein folds not yet detected in viruses (51) . We identified two FSFs that are part of bacterial carboxysomes: (i) "Ccmk-like" (d.58.56) and (ii) "EutN/CcmL-like" (b.40.15) FSFs. Both had an f value of 0 in sampled viral proteomes, confirming a lack of overlap between carboxysomes and viral capsids. However, this could also be explained by the loss of an ancient capsid protein fold in modern viruses or an outcome of sampling biases (49) . Alternatively, it is possible that viruses harboring similar folds exist in nature but remain to be discovered. An interesting analogy could also be made for eukaryotes where histone monomers assemble around DNA to produce chromatin structure. Remarkably, this process is mediated by histone chaperones that harbor the "jelly-roll" fold (52) that is abundant in icosahedral viruses. Thus, on the basis of current knowledge, although most viral capsid/coat FSFs have no SCOP structural relatives and lack cellular homologs (Table 3) , rare capsid structural homologies in cellular proteomes suggest either instances of virus-tohost HGT or relics of the ancient coexistence of cells and viruses.