Primer: Functions and evolution of viral proteins

Viruses encode an enormous variety of proteins that jointly comprise the largest pool of protein diversity on Earth. At coarse grain, the viral pan-proteome can be partitioned into four classes of proteins that differ in their evolutionary conservation, spread across the virosphere, and broadly defined functionality: (i) viral hallmark proteins (VHPs) that are broadly conserved across different realms of viruses, (ii) proteins responsible for core viral functions, such as replication, expression, and virion structure, but are more narrowly represented within a single virus realm, kingdom, or phylum, (iii) fast-evolving proteins involved in virus-host interactions, particularly counter-defense, that are typically conserved only in narrow groups of viruses, (iv) "dark matter," that is, proteins without detectable homologs or known functions, typically shared only by closely related viruses. Apart from the few VHPs that might descend from the primordial protein pool, most of the viral proteins are derived from cellular ancestors, via recruitment of proteins with activities relevant for virus replication, and extensive exaptation. The recruitment of cellular proteins for roles in viral reproduction follows a logic dictated by the functionalities that are relevant for viruses. Thus, different groups of viruses often convergently capture distinct, sometimes unrelated proteins, providing similar activities, for example, polymerases, helicases, and proteases of different families. Recent advances in protein structure prediction and analysis provide unprecedented insights into the organization and evolution of the viral pan-proteome.