Extended Data Fig. 6: Evolutionary history of delta-virus-like agents.

a Consensus structures (weighted nucleotide conservation threshold of 90%) of delta virus ribozymes, including the 14 genomes described in this work. b Consensus structures of the two hammerhead ribozyme families (type III and extended-type III³⁹) detected in epsilon and zeta agents. Most positions of epsilon and zeta motifs are sequence conserved for each ribozyme family. c MSA of the predicted antigen (N-term domain) from delta and epsilon agents (genomes detected in this study are indicated with a red asterisk). The antiparallel coiled-coil of the HDV is delimited with a grey box, and conserved residues involved in hydrophobic interactions are shown at the bottom⁴⁰, supporting a highly divergent connection between delta and epsilon genomes. d Human HDV delta virus is known to contain a viroid-like domain related to the Pospiviroidae family of plant viroids. Both families of agents conserve a tertiary structure reminiscent of the E-loop 5S rRNA (nucleotides in green) and are replicated by the RNA Pol II of the host⁴¹. Pospiviroids, despite lacking hhrbzs, share with zeta genomes a small rod structure, and in some cases, the presence of predicted endless tandem-repeat ORFs, most notably in both polarities of numerous variants of the Hop Stunt Viroid (HSVd). Whereas viroids have been historically regarded as non-protein-coding RNAs, our reported observations warrant further investigation.