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Posted by RJG on April 15, 2013  •  Paleovirology

spiral clock

What is paleovirology?

Paleovirology addresses the long-term evolutionary history of viruses. Traces of this history are embedded in the biodiversity of contemporary species. For example, the architectures of proteins and nucleic acids contain information about the early evolution of viruses [1, 2], and in host species, the sequences of 'antiviral' genes contain the signatures of their epic evolutionary conflicts with viral antagonists [3, 4, 5].

Another means by which the ancient history of viruses can be investigated is through recovery of the viral 'fossil record' [6, 7, 8]. Eukaryotic genomes contain thousands of DNA sequences that are derived from ancient viruses. These endogenous viral elements (EVEs) arise when infection causes genetic material derived from a virus to become integrated into the host germline, such that viral genes can be inherited as host alleles. Over millions of years, repeated genome invasions by viruses have occurred, and some of the resulting EVEs have become fixed in the host germline - these DNA sequences are viral fossils.

Recent years have seen vast advances in the affordability and power of DNA sequencing technologies, and genome sequence data are accumulating at an accelerating pace. This deluge of sequence data provides unprecedented scope for paleovirological studies of the virus fossil record.

Discovery of the virus fossil record

The capacity of some viruses to integrate into the genomes of host cells has been recognized since the 1960s. Experiments during this period demonstrated that certain types of viruses can cause cancer through mechanisms that involve the integration of viral genetic material into the nuclear genome of the host cell - a discovery for which Baltimore, Dulbecco, and Temin were later awarded the Nobel prize. However, the initial interest in this phenomenon focused almost exclusively on it's association with cancer, and while the idea that viruses might cause neoplasms by integrating into somatic cells was readily accepted by scientists, the notion of viral genetic material stably entering the host germline was initially considered outlandish [9].

Nonetheless, studies using DNA hybridization-based approaches soon demonstrated that sequences derived from retroviruses occur naturally in many vertebrate genomes, and an interest in using these sequences as a basis for investigating the deeper evolutionary history of retroviruses began to emerge. Early studies using hybridization-based approaches, revealed broad trends in the distribution of endogenous viral sequences across host species. For example, working in the early 1970s, Todaro and Benveniste were able to establish evidence for an ancient cross-species transmission event in which Gammaretroviruses were transmitted between primate and feline hosts [10]. This discovery, and many similar advances from this early period, have subsequently been consolidated by genomic and molecular phylogenetic approaches [11].

The relevance of paleovirology to contemporary biology and medicine

Although paleovirology focuses on ancient viruses, it nonetheless has an important role to play in directing our approaches to modern viruses and the threats they pose. In the era of 'big data' and genomics, it has become feasible to begin characterising the genetic diversity of viruses on a large scale, and using this data to establish measures of 'viral risk' that are founded in empirically derived ecological and evolutionary principles [12]. Paleovirology is an important component of this endeavour, in the same way that paleontology is an essential component of efforts to recover and comprehend the biology of cellular organisms in terms of their evolutionary history.

Developing an understanding the history of viral diseases can guide the development of new strategies for disease control, particularly where traditional approaches have proved ineffective or inappropriate. It can also underpin the rationale of efforts to protect endangered species from viral disease, both in the wild and in captive breeding programs.


1.  Sun, F.J. and G. Caetano-Anolles. (2008) Evolutionary patterns in the sequence and structure of transfer RNA: early origins of archaea and viruses. PLoS Comput Biol 4(3): p. e1000018. [view]

2.  Nasir, A., K.M. Kim, and G. Caetano-Anolles. (2012) Giant viruses coexisted with the cellular ancestors and represent a distinct supergroup along with superkingdoms Archaea, Bacteria and Eukarya. BMC Evol Biol 12: p. 156. [view]

3.  Emerman, M. and H.S. Malik. (2012) Paleovirology--modern consequences of ancient viruses. PLoS Biology 8(2): p. e1000301. [view]

4.  Sawyer, S.L., M. Emerman, and H.S. Malik. (2004) Ancient adaptive evolution of the primate antiviral DNA-editing enzyme APOBEC3G. PLoS Biology 2(9): p. E275. [view]

5.  Newman, R.M., L. Hall, M. Connole, G.L. Chen, S. Sato, E. Yuste, W. Diehl, E. Hunter, A. Kaur, G.M. Miller, and W.E. Johnson. (2006) Balancing selection and the evolution of functional polymorphism in Old World monkey TRIM5alpha. PNAS 103(50): p. 19134-9. [view]

6.  Gifford R.J. and M. Tristem. (2003). The evolution, distribution and diversity of endogenous retroviruses. Virus Genes 26:291-315 [view]

7.  Katzourakis A. and R.J. Gifford. (2010) Endogenous viral elements in animal genomes. PLoS Genetics 6(11): e1001191. [view]

8.  Feschotte, C., and C. Gilbert. (2012) Endogenous viruses: insights into viral evolution and impact on host biology. Nature Reviews Genetics 13:283-96. [view abstract]

9.  Weiss R.A. (2006) The discovery of endogenous retroviruses. Retrovirology. 3;3:67. [view]

10.  Benveniste R.E, Todaro G.J.(1974) Evolution of C-type viral genes: inheritance of exogenously acquired viral genes. Nature 252(5483):456-9. [view abstract]

11.  van der Kuyl AC, Dekker JT, Goudsmit J. (2009) Discovery of a new endogenous type C retrovirus (FcEV) in cats: evidence for RD-114 being an FcEV(Gag-Pol)/baboon endogenous virus BaEV(Env) recombinant. J Virol. 28(2):89-100. [view abstract]

12.  Gifford R.J. (2012) Viral Evolution in Deep Time - Lentiviruses and Mammals. Trends in Genetics Feb;28(2):89-100. [view abstract]