Which Came First: The Virus or the Host?

They existed 3.5 billion years before humans evolved on Earth. They’re neither dead nor alive. Their genetic material is embedded in our own DNA, constituting close to 10% of the human genome. They can attack most forms of life on our planet, from bacteria to plants to animals. And yet, if it wasn’t for them, humans might never have existed.

3D structure of a coronavirus, viral evolution
A depiction of the shape of coronavirus as well as the cross-sectional view. The image shows the major elements including glycoproteins, viral envelope and helical RNA. This file is licensed under the Creative Commons Attribution-Share Alike 4.0 International license.

No, that’s not the blurb for a new Hollywood blockbuster, although recent developments have proven, once again, that truth is decidedly more bizarre than fiction. Now that “coronavirus” has become a household word, the level of interest in all things virus-related is growing at an unprecedented rate. At the time of writing, coronavirus and COVID-19 topics dominated search traffic on Google, as well as trends on social media. A recent FAQ on this blog addresses many of the questions we hear on these topics.

The virus officially known as SARS-CoV-2 (the disease it causes is called COVID-19) belongs to the larger family of coronaviruses, or Coronaviridae. All viruses consist of a piece of nucleic acid—DNA or RNA—enclosed within a protein coat known as the capsid. In the case of coronaviruses, the nucleic acid is a single-stranded RNA molecule. Additionally, coronaviruses are characterized by an outer envelope consisting of a lipid bilayer, derived from the membrane of the host cell infected by the virus. In this lipid coat are embedded viral glycoproteins, some of which are attractive targets for therapeutic efforts (1).

Before the Origin of Species

Viral evolution (and abiogenesis in general) is one of those fascinating branches of science where we often face a sobering realization: what we know is how much we don’t know (2). For example, the presence of a lipid envelope would imply that coronaviruses evolved after cells did, since the host cell is the source of lipids. It also follows, from the definition of a virus as an obligate parasite, that it needs a host cell in order to replicate. But was that always the case? To answer the question definitively, we’d need a time machine that could take us back around 4 billion years—give or take a few hundred million.

Traditionally, theories of viral evolution belong to one of three groups: the virus-first hypothesis, the regression hypothesis and the escaped genes hypothesis.

The virus-first hypothesis

According to this hypothesis, viruses evolved early in Earth’s history from fundamental replicative molecules that formed in the “primordial soup” as the planet began cooling. These molecules also led to the evolution of cellular organisms—the viral hosts—either in parallel or at a later stage of evolution. A foundational part of this hypothesis is challenging the dogma that viruses must always exist as particles of nucleic acids surrounded by proteins (3). Early viroids could have existed simply as free-floating pieces of nucleic acids. The variety of ways in which viruses store their genomic information (single- or double-stranded DNA or RNA), in contrast with cellular organisms, lends credence to the idea that viruses emerged before the appearance of the last universal cellular ancestor (LUCA) (4).

Among other reasons, this hypothesis is attractive because it’s compatible with another popular abiogenetic hypothesis: the RNA world. In this scenario, the earliest precursors of life were RNA molecules that were able to self-replicate. The discovery of RNA enzymes or ribozymes fueled a surge of interest in this hypothesis. Over the years, the RNA world hypothesis has gained its share of detractors. However, a recent study showing that ribonucleotides—the building blocks of RNA—could be synthesized in a primordial soup environment provided a shot in the arm for the RNA world enthusiasts (5).

The regression hypothesis

Also known as the reduction or degeneracy hypothesis, this scenario posits that viruses resulted from cellular ancestors that took an evolutionary step backward and lost the ability to replicate on their own. These protocells were forced into a lifestyle of obligate parasitism in order to survive and, ultimately, ended up as viruses. The discovery of two giant viruses, members of the Mimiviridae family, lent support to this hypothesis (6). These viruses, with double-stranded DNA genomes of 1.4-1.5Mb that encode over 1,400 proteins, were isolated from amoebae. Their repertoire of proteins included many components of the translation machinery and energy production systems—rarely observed in most other viruses. These observations suggested that the giant viruses evolved by regression from ancestors that had a complete set of genes, resembling cellular life forms rather than modern-day viruses.

The “escaped genes” hypothesis

This hypothesis proposes that viruses evolved from genes that “escaped” from cellular organisms at multiple stages during the evolution of early life. These genes gave viruses the basic abilities for semiautonomous (selfish) replication and infectivity. Later studies expanded on the evidence for this hypothesis to suggest that viruses evolved not from modern cells but from primordial ancestors that predated LUCA (7).

Back to the Future

These three hypotheses of viral origin have been debated over many years and have spawned alternate hypotheses that combine different elements of each. Each hypothesis presents a different timeline for viral origins, ranging from viruses emerging well before cellular life to evolution after the formation of cells. Recently, a chimeric scenario has been proposed in which viruses derived their replication machinery from different types of primordial genetic elements but obtained the structural proteins required for capsid formation from their cellular hosts (8).

Future studies will, no doubt, add more variations on the three fundamental themes of viral origins. The current SARS-CoV-2 pandemic has highlighted the deadly properties of pathogenic viruses, and yet many viruses play commensal or even mutualistic roles (9). One thing is clear: viral evolution is inextricably linked with our own. The quest to understand viral origins should also bring new insights into how other life forms adapted and responded to the challenge posed by these enigmatic parasites. Broadening our base of knowledge should equip us to better handle the next pandemic.

Read how Promega is supporting scientists working to understand the molecular mechanisms by which emerging viruses infect humans and animals, and to develop accurate detection methods. Visit the Coronavirus Detection and Assay Development resource page.


  1. Schoeman, D. and Fielding, B.C. (2019) Coronavirus envelope protein: current knowledge. Virology J. 16, 69.
  2. Pross, A. and Pascal, R. (2013) The origin of life: what we know, what we can know and what we will never know. Open Biol. 3, 120190.
  3. Bandea, C. (2009) The origin and evolution of viruses as molecular organisms. Nature Precedings DOI: 10.1038/npre.2009.3886.1.
  4. Holmes, E.C. (2011) What does virus evolution tell us about virus origins? J. Virol. 85, 5247.
  5. Becker, S. et al. (2019) Unified prebiotically plausible synthesis of pyrimidine and purine RNA ribonucleotides. Science 366, 76.
  6. Abrahão, J. et al. (2018) Tailed giant Tupanvirus possesses the most complete translational apparatus of the known virosphere. Nature Comm. 9, 749.
  7. Krupovic, M. and Koonin, E.V. (2017) Multiple origins of viral capsid proteins from cellular ancestors. Proc. Natl. Acad. Sci USA. DOI: 10.1073/pnas.1621061114.
  8. Krupovic, M. et al. (2019) Origin of viruses: primordial replicators recruiting capsids from hosts. Nature Rev. Microbiol. 17, 449.
  9. Roossinck, M. and Bazán, E.R. (2017) Symbiosis: viruses as intimate partners. Annu. Rev. Virol. 4, 123.

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Ken Doyle
Ken is a science writer at Promega Corporation. Although his PhD is in molecular biology, he enjoys researching and writing about everything from M-theory to graptolites. When he's not spending time with family or serving his canine and feline overlords, Ken engages in a quest for a mythical creature known as "spare time". If he succeeds, he hopes to return to writing fiction so he can keep his brain in balance.


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