Paleovirology: connecting recent and ancient viral evolution
Keywords: Foamy viruses
Endogenous viral elements
Time dependent rate phenomenon

Endogenous viral elements, or viral genomic fossils, have proven extremely valuable in the study of the macroevolution of viruses, providing important, and otherwise unobtainable, insights into the ancient origin of viruses, and how their ancestors might have co-evolved with their hosts in the distant past. This type of investigation falls within the realm of paleovirology—the study of ancient viruses. Investigations of extant viruses and paleovirological analyses, however, often give conflicting results, especially those concerning viral evolutionary rates and timescales. Reconciling these two types of analyses is a necessary step towards a better understanding of the overall long-term evolutionary dynamics of viruses. The main study system of this thesis is foamy viruses (FVs). FVs are characterised by their stable co-speciation history with their hosts, allowing their evolutionary dynamics to be modelled and investigated over various timescales. This unique evolutionary feature makes FVs one of the best subjects for connecting recent and ancient viral evolution. The work here reports the discovery of several endogenous mammalian FVs, and examines how mammalian FVs co-evolve with their hosts. Analyses reveal a co-diversifying history of the two that could be dated back to the basal radiation of eutherians more than 100 million years ago. However, a small number of ancient FV cross-species transmissions could still be found, mostly involving New World monkey FVs. Based on this extended FV-mammal co-speciation pattern, this thesis investigates the long-term evolutionary rate dynamics of FVs, and shows that the rate estimates of FV evolution appear to decrease continuously as the rate measurement timescale increases, following a power-law decay function. The work presented here also shows that this so-called 'time-dependent rate phenomenon' is in fact a pervasive evolutionary feature of all viruses, and surprisingly, the rate estimates of evolution of all viruses seem to decay at the same speed, decreasing by approximately half for every 3-fold increase in the measurement timescale. Based on this power-law rate-decay pattern, we could infer evolutionary timescales of modern-day lentiviruses that are consistent with paleovirological analyses for the first time. Finally, this thesis reports the discovery of basal FV-like endogenous retroviruses (FLERVs) in amphibian and fish genomes. Phylogenetic analyses reveal that the progenitors of ray-finned fish FLERVs co-diversify broadly with their fish hosts, but also suggest that there might have been several ancient viral cross-class transmissions, involving lobe-finned fish, shark, and frog FLERVs. Again, by using the power-law rate-decay model, analyses in this thesis suggest that this major retroviral clade has an ancient Ordovician marine origin, originating together with their jawed vertebrate hosts more than 450 million years ago. This finding implies that the origin of retroviruses as a whole must be in the early Paleozoic Era, if not earlier. The results presented here bridge ancient and recent viral evolution.