Paleovirology - ghosts and gifts of viruses past

Abstract

The emerging field of paleovirology aims to study the evolutionary age and impact of ancient viruses (paleoviruses) on host biology. Despite a historical emphasis on retroviruses, paleoviral 'fossils' have recently been uncovered from a broad swathe of viruses. These viral imprints have upended long-held notions of the age and mutation rate of viruses. While 'direct' paleovirology relies on the insertion of viral genes in animal genomes, examination of adaptive changes in host genes that occurred in response to paleoviral infections provides a complementary strategy for making 'indirect' paleovirological inferences. Finally, viruses have also impacted host biology by providing genes hosts have domesticated for their own purpose.

Figure 1. Deducing age of paleoviruses based on insertion in host genomes

(A) When a viral imprint is found in exactly the same genomic location in two species' genomes, then the paleoviral insertion is inferred to have occurred in a common ancestor. We can infer the minimum age of the paleovirus based on speciation times of the two most distantly related host species that bear the 'orthologous' provirus. (B) If the insertions are seen in 'non-orthologous' positions, there is a possibility that this reflects unequal lineage sorting in which Species A inherited one EVE while Species B inherited the other, despite the fact that both EVEs resulted from the same episode of infection in an ancestral species. More likely though, this reflects independent insertions after the species had already separated. Other corroborative evidence (e.g. estimates of mutations) is needed to formally distinguish between these two possibilities.

Figure 2. Apparent discordance in short versus long-term evolutionary rates of viruses

As viruses evolve over long periods of time, bulk lineages (bold lines) diverge and diversify. However, within each lineage, there are limits to which a viral lineage can evolve before it begins to lose function. As a result, given enough time and mutational saturation, long-term evolution of viruses may be bounded by functional constraints (dotted line represents evolutionary trajectory of a single viral lineage). As a result, any paleoviral fossils (denoted by 'skull and bones') derived from this 'trunk' of evolution will reflect the evolutionary boundedness of mutational space. In contrast, short-term mutation rates are less affected by mutational saturation and may not reflect the 'purifying selection' imposed long-term on viral lineages[13]. Thus, even though they occur at vastly different time-scales, extant viruses evolving under short-term mutation rates can be compared to, and used to identify, ancient paleoviral fossils.