Nucleic and Amino Acid Sequences Support Structure-Based Viral Classification

Abstract

Viral capsids ensure viral genome integrity by protecting the enclosed nucleic acids. Interactions between the genome and capsid and between individual capsid proteins (i.e., capsid architecture) are intimate and are 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 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 similarities, suggesting that the 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.IMPORTANCE Viral capsids protect nucleic acid genomes, which in turn encode capsid proteins. This tight coupling of protein shell and nucleic acids, together with strong functional constraints on capsid protein folding and architecture, leads to the hypothesis that capsid protein-coding nucleotide sequences may retain signatures of ancient viral evolution. We have been able to show that this is indeed the case, using the major capsid proteins of viruses forming icosahedral capsids. Importantly, we detected similarity at the nucleotide level between capsid protein-coding regions from viruses infecting cells belonging to all three domains of life, reproducing a previously established structure-based classification of icosahedral viral capsids.

Evolution of the PRD1-adenovirus lineage: a viral tree of life incongruent with the cellular universal tree of life

“…Phylogenetic analyses were performed separately on the MCP and the pATPase using the resulting datasets within the maximum likelihood (ML) framework. DJR eukaryoviruses were clearly separated from archaeoviruses and bacterioviruses in both trees, in agreement with previous observations made using pairwise sequence similarities or comparative structural analyses ( 11 , 24 ). In particular, unlike the result obtained with the sequence similarity network, members of the Lavidaviridae were grouped with other eukaryoviruses in the pATPase tree.…”

“…In a phylogenetic tree based on the common core of the MCP published in 2013, the viruses of the DJR PRD1-adenovirus were divided into three groups: one corresponding to Adenoviruses, another grouping NCLDVs (represented by two members) with Lavidaviridae , and the third one including viruses infecting Archaea and Bacteria ( 11 ). Furthermore, the evolutionary relationships among the PRD1-adenovirus lineage were recently investigated using pairwise sequence similarities between DJR viruses ( 20 , 24 ). These analyses demonstrated that there are evolutionary links between archaeoviruses and bacterioviruses as well as eukaryoviruses and bacterioviruses.…”

Diversity and evolution of the emerging Pandoraviridae family

“…No protein even remotely similar to the usually abundant major capsid protein (MCP), a predicted DNA-binding core protein, or a DNA-packaging ATPase, hallmarks of most eukaryotic large DNA viruses, was detected. In particular, a P. salinus hypothetical protein (previously ps_862 now reannotated psal_cds_450) recently suggested by Sinclair et al 16 to be a strong major capsid protein candidate was not detected in the P. salinus virions, nor its homologs in the other strain proteomes. This result emphasizes the need for the experimental validation of computer predictions made from the "twilight zone" of sequence similarity.…”

A Novel Type of Polyhedral Viruses Infecting Hyperthermophilic Archaea

“…Besides the MCPs, these viruses employ similar virion assembly and maturation as well as genome packaging mechanisms, which are not found in viruses outside this virus assemblage (46). The second architectural class encompasses highly diverse dsDNA viruses with the vertical double-jelly-roll (DJR) MCPs, including members of the bacterial virus families Corticoviridae and Tectiviridae, archaeal viruses of the family Turriviridae, and eukaryotic viruses of the families Adenoviridae and Lavidaviridae as well as the proposed order "Megavirales" that comprises most of the large and giant eukaryotic viruses (47)(48)(49). Most viruses within this class contain an internal membrane vesicle located between the protein capsid and the dsDNA genome and carry genes that encode homologous A32-like genome packaging ATPases not found in other virus groups.…”