We report a phylogenetic study of viroids, some plant satellite RNAs, and the viroidlike domain of human hepatitis 8 virus RNA. Our results support a monophyletic origin of these RNAs and are consistent with the hypothesis that they may be "living fossils" of a precellular RNA world. Moreover, the viroidlike domain of human hepatitis 8 virus RNA appears closely related to the viroidlike satellite RNAs of plants, with which it shares some structural and functional properties. On the basis of our phylogenetic analysis, we propose a taxonomic classification of these RNAs.assumed an intracellular mode of existence sometime after the evolution of cellular organisms.Implicit in this proposal is the possibility that all viroids and viroidlike RNAs may have been derived from a common ancestor. To obtain evidence for or against this proposition, we have conducted a phylogenetic analysis of these small pathogenic RNAs and report here that our results are consistent with a monophyletic origin of viroids and viroidlike satellite RNAs, as well as possibly of the viroidlike domain of HDV RNA.Viroids, subviral pathogens of higher plants, are small (246-375 nucleotide residues), unencapsidated, single-stranded, circular RNAs characterized by highly base-paired, rodlike secondary structures (1). Viroids do not code for any proteins, yet they replicate autonomously (without the assistance of helper viruses) in susceptible cells. Viroidlike satellite RNAs resemble viroids, but they are found within the capsids of specific helper viruses required for their replication (2). Human hepatitis 8 virus (HDV) RNA is a circular RNA requiring hepatitis B virus as a helper virus for packaging and transmission (3). HDV RNA contains a region, termed the viroidlike domain, with significant similarities with viroid and viroidlike satellite RNAs (4). Viroids, viroidlike satellite RNAs, and HDV RNA appear to replicate via oligomeric RNA intermediates by some type of rolling-circle mechanism (2-6).Several hypotheses have been advanced to explain the evolution of viroids. It has been suggested, for example, that viroids may have originated from retroviruses or transposable elements by deletion of interior sequences (7), that they may represent escaped introns (8, 9), or that they have evolved comparatively recently from hypothetical "antenna" or "signal" RNAs, which eukaryotic cells are assumed to interchange (10).With the demonstration that certain RNAs have catalytic properties (11,12), the idea that RNA preceded DNA as a carrier of genetic information has gained support. Most recent models for self-replicating precellular RNAs assume the existence of primitive RNA enzymes with properties that are derived from extant self-splicing introns (13,14). Because one viroid, all known viroidlike satellite RNAs, and the viroidlike domain of HDV RNA are self-cleaving (3, 15, 16), it is equally plausible to consider these RNAs as relics of the RNA world, thus leading to an alternative hypothesis for the evolution of viroids and viroidlike satellite R...