Nucleic and amino acid sequences support structure-based viral classification

Viral capsids ensure viral genome integrity by protecting the enclosed nucleic acids. Interactions between the genome, capsid and between individual capsid proteins (i.e. “capsid architecture”) are intimate and expected to be characterized by strong evolutionary conservation. For this reason, a capsid structure-based viral classification has been proposed as a way to bring order to the viral universe. The seeming lack of sufficient sequence similarity to reproduce this classification has made it difficult to reject structural convergence as the basis for the classification. We reinvestigate whether the structure-based classification, for viral coat proteins making icosahedral virus capsids, is in fact supported by previously undetected sequence similarity. Since codon choices can influence nascent protein folding cotranslationally, we have searched for both amino acid and nucleotide sequence similarity. To demonstrate the sensitivity of the approach, we identify a candidate gene for the Pandoravirus capsid protein. We show that the structure-based classification is strongly supported by amino acid and also nucleotide sequence similarity, suggesting that similarities are due to common descent. The correspondence between structure-based and sequence-based analyses of the same proteins shown here allow them to be used in future analyses of the relationship between linear sequence information and macromolecular function, as well as between linear sequence and protein folds