News Release

Scientists present evidence for a billion-years arms race between viruses and their hosts

Findings add to our understanding of the deep evolutionary history of the highly diverse Bamfordvirae kingdom of viruses

Peer-Reviewed Publication


Researchers have proposed a new evolutionary model for the origin of a kingdom of viruses called Bamfordvirae, suggesting a billion-years evolutionary arms race between two groups within this kingdom and their hosts.

Their study, published today as a Reviewed Preprint in eLife, provides what the editors say are convincing analyses that advance our understanding of the deep evolutionary history of viruses, the interaction between viruses and the first eukaryotes (organisms with cells that include a nucleus), and the diversification of viral lineages.

Viruses in the kingdom Bamfordvirae make up one of the most diverse groups that infect living organisms. They include the Nucleocytoplasmic Large DNA viruses (NCLDVs; the largest viruses characterised to date), virophages (viral parasites of other viruses), adenoviruses (common viruses that cause cold and flu-like symptoms), and Mavericks and Polinton-like viruses (both virus-like mobile genetic elements that colonise the genomes of their hosts).

There are two main hypotheses for the origins of these viruses: the ‘nuclear-escape’ and ‘virophage-first’ hypotheses. The nuclear-escape hypothesis says that a Maverick-like ancestor originated with hosts (endogenous), escaped from the host cell nucleus and gave rise to adenoviruses and NCLDVs. In contrast, the virophage-first hypothesis suggests that NCLDVs co-evolved with early virophages. Mavericks then evolved from virophages that became endogenous, with adenoviruses escaping from the host nucleus at a later stage.

“Despite these proposed scenarios, the diversification of viruses in the Bamfordvirae kingdom remains a major open question in virus evolution. To gain a better understanding of their history, we wanted to test the predictions made by both the nuclear-escape and virophage-first models, and consider alternative scenarios regarding the origin of different lineages,” says José Gabriel Niño Barreat, Postdoctoral Research Assistant at the University of Oxford, UK. Barreat is a co-author of the study alongside Aris Katzourakis, Professor of Evolution and Genomics at the University of Oxford’s Department of Biology.

Barreat and Katzourakis used two hypothesis-testing methods (maximum-likelihood and Bayesian frameworks) to compare the plausibility of the nuclear-escape versus alternative evolutionary scenarios. They focused on four key proteins shared by viruses in this lineage which are involved in the formation of viral capsids: major and minor capsid proteins, DNA-packaging ATPase, and protease. They applied another two methods that use genetic data to estimate rooted phylogenies, to infer the evolutionary trajectory of the different lineages. Then, they assessed whether adenoviruses and NCLDVs descended from a common ancestor, as predicted by the nuclear-escape scenario.

Their analyses revealed strong evidence against a sister relationship between adenoviruses and NCLDVs, as suggested by the nuclear-escape hypothesis. Instead, the findings suggest that adenoviruses descended from a common ancestor with Mavericks, to the exclusion of NCLDVs. At odds with a virophage-first scenario, the researchers found that the most recent common ancestor of Mavericks and adenoviruses was not a virophage. However, their work does not rule out the virophage-first hypothesis completely, making it the one best supported by current phylogenetic analyses.

Additionally, their work provides support for the positioning of the Bamfordvirae ancestral root between virophages and the other viral lineages. This positioning pointed the team towards a new model for the evolutionary origins of these viruses.

“The model proposes that the Bamfordvirae ancestor did not originate from an invasion of the eukaryotic cell nucleus, and that it was a non-virophage DNA virus with a small genome,” says co-author Aris Katzourakis. “The lifestyle of virophages would have evolved at a later stage as these became specialised parasites of the ancestral NCLDVs.” Katzourakis adds that the relative timing of events suggests the most recent common ancestor of the Bamfordvirae kingdom existed more than a billion years ago, extending to the initial stages of eukaryotic life. However, an absolute timescale for the precise dating of these events is not currently available.

Another limitation of the study is that the phylogenetic signal in the protein data analysed may have been obscured by the deep divergences and extreme diversity in this lineage. However, the authors were able to robustly distinguish between alternative scenarios, and the focus on the origin and development of the viral capsid provides a simple way to explain the available data.

“This work contributes to our knowledge on how viruses evolve different evolutionary strategies, for example to become parasites of other viruses like virophages, or viral giants like NCLDVs,” Barreat says. “As well as playing important roles in Earth's ecosystems, it is becoming increasingly clear that viruses may have contributed to major evolutionary transitions during the history of life. Therefore, understanding the deep evolutionary history of viruses provides more context for these ancient interactions and the actors involved.”

“Unravelling the interactions between viruses and their hosts provides a window into the deep evolutionary past that is illuminating the origins of both of these biological entities,” Katzourakis concludes.



The Reviewed Preprint, ‘A billion years arms-race between viruses, virophages and eukaryotes’, is available to view at Contents, including text, figures and data, are free to reuse under a CC BY 4.0 license.

Author contact

Aris Katzourakis (co-author), Professor of Evolution and Genomics
University of Oxford’s Department of Biology
+44 (0)1865 281847

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