Cellular homologs of the double jelly-roll major capsid proteins clarify the origins of an ancient virus kingdom

Significance Viruses are the most abundant biological entities on Earth and ubiquitous parasites of cellular life forms. The general scenario for the origin of viruses involves evolution from nonviral replicators, such as plasmids and transposons, via recruitment of host proteins for virion formation. One of the most common virion core components, the double jelly-roll major capsid protein of a broad variety of viruses with double-stranded DNA genomes, so far has been thought to represent a virus innovation. However, we present evidence, obtained by protein structure comparison, that this type of virus capsid protein also evolved from a cellular ancestor, a distinct family of carbohydrate-active enzymes. These findings reinforce the chimeric scenario of virus origin.