Endless Forms Most Viral

Perhaps more than any other biological discipline, the study of animal viruses is confined to the present. Virions are simply not the stuff of which robust fossils are made. Phylogenetic analysis can help by revealing deep relationships between extant viral lineages, yet such reconstructions lack detail (telling us nothing about transitional or extinct viral forms, the movement of viruses between species, or the timing of major events in viral evolution), and molecular clock estimates are notoriously imprecise when applied to viruses [1]. Until recently, ancient endogenous retroviruses (ERVs) were the closest thing to a fossil record available to scientists with a proclivity for combining virology and natural history. Happily, a trio of recent studies appearing in PLoS Genetics [2], PLoS Biology [3], and PLoS Pathogens [4] reveal an unexpected wealth of non-retroviral virus sequences embedded in the genome sequence databases, a virtual equivalent of the Burgess Shale, ripe for excavation by eager paleovirologists. Retroviral infection occasionally results in the deposition of a provirus in a host’s germline DNA. While germline integration of a provirus may be an exceedingly rare event, across the great expanse of evolutionary time millions of ERV loci have accumulated in animal genomes. Because retroviruses replicate through an integrated DNA intermediate, it is not difficult to imagine how ERVs are generated. For other animal viruses, which do not normally integrate their genomes into host DNA, the formation of germline insertions should be far less likely. Nonetheless, reports of non-retroviral specimens being unearthed from the genomes of animal species are on the rise. Notable examples include functional expression of nudivirus-related structural genes in the genomes of parasitic wasps [5]; Ebolavirus-like sequences, related to modern filoviruses, present in multiple mammalian genomes [6]; and sequences resembling the Bornavirus nucleoprotein gene (N) in the genomes of various mammals including primates, rodents, and elephants [7]. Even some herpesviruses have a propensity for occasional germline insertion and thus, the potential for vertical inheritance [8]. Now, Belyi et al. [4] and Katzourakis and Gifford [2], have unearthed diverse collections of non-retroviral sequences buried in whole genome sequence data from an impressive array of host organisms, including mammals, marsupials, birds, rodents, and insects, using modern viral sequences as bioinformatic probes. A third study from Gilbert and Feschotte specifically reevaluates the macroevolution of hepadnaviruses based on the sequence and distribution of hepadnavirus-like fossils in the genomes of passerine birds [3]. To cope with this newfound abundance, the authors of one of the studies suggest the acronym EVE (for endogenous viral element) as a general term to encompass all virus-derived genomic loci [2]. Two of the studies also took a closer look at a previously described class of EVEs, called EBLNs (for endogenous Bornavirus-like N genes) [2,4,7]. While most EVEs were either defective at the time of insertion or rendered functionless by the accumulation of random mutations over the course of millions of years, EBLNs are striking in retaining largely intact protein-coding sequences. In fact, in silico simulations of EBLN evolution estimate that these elements should have accumulated ,10–20 stop codons since the time of genome insertion. That the EBLN coding sequences appear relatively unscathed suggests that these particular elements provide (or at times provided) a selectively advantageous function, subjecting them to purifying selection. The possibility is not without precedent: for example, at least one human ERV has evolved to provide a cellular function [9], and there are several examples of ERVs that have been subverted by host evolution to serve as inhibitors of retroviral infection [10–14]. As a group, viruses are polyphyletic, as evidenced by the variety of unique ge-