The place Do Viruses Come From?

All cellular life, from single-celled bacteria to towering trees, can trace its origins back to a single forerunner that existed roughly four billion years ago, the last universal common ancestor (LUCA).¹ The story of viruses—an infectious collection of genetic material inside a protein or lipid shell—is far less straightforward. Viruses arose in not one but at least seven separate events, each one giving rise to a “realm” of viruses that share a common lineage.² Scientists have put forward a bevy of theories to explain how each realm came into existence. However, new genome sequencing data is compelling virologists to rework virus family trees by splitting realms apart and rewriting the history of virus evolution.³

Did Viruses Appear Before Cells?

To investigate the origins of viruses, scientists look back to the earliest stages of life on Earth. Even though all modern viruses rely on cells for their replication, one idea, known as the “virus-first hypothesis,” proposes that viruses appeared before cells came into existence.⁴ This scenario could apply to at least five of the seven viral realms that infect every domain of life. Take the Duplodnaviria realm, for example: Its DNA viruses are found in archaea, bacteria (as bacteriophages), and eukaryotes (including herpesviruses). Because these hosts are so fundamentally different, it’s unlikely that a virus infecting one could have simply evolved to infect another. This suggests that the ancestor of Duplodnaviria must have already existed by the time of LUCA or perhaps even earlier, lending support to the virus-first hypothesis.

Some viral realms infect only specific groups of organisms, which suggests they arose after certain branches of life had already evolved, rather than dating all the way back to LUCA. For instance, viruses in the Adnaviria realm are found exclusively in archaea, implying they likely emerged after archaea appeared around 3.8 billion years ago, said Murilo Zerbini, president of the International Committee on Taxonomy of Viruses (ICTV).⁵ However, taking a closer look at viral proteins can cast doubt on that conclusion. For example, viruses in the Ribozyviria realm only infect eukaryotes, so it would seem logical that they evolved after eukaryotes emerged about 1.7 billion years ago.⁶ Yet, these viruses possess ribozymes—RNA-based enzymes—that trace their origins back to the ancient RNA world, hinting that they may be much older, possibly predating cellular life itself, Zerbini noted.

Corroborating the virus-first hypothesis is challenging. Tracing lineages back four billion years involves such large uncertainties that it’s impossible to tell which came first, the virus or the cell. To complicate matters further, scientists have found that every viral realm contains genes related to those in cellular DNA.⁷ This makes it hard to determine if viruses were precursors to cells, if they both arose independently and later exchanged genes—which both fit the virus-first model—or if viruses actually originated from cells. Regardless of the answer, viruses and cells have profoundly influenced each other’s evolution.

Viruses May Have Come from a Minimalist Cell

How could viruses, typically harboring only a handful of genes, have emerged from cells equipped with thousands of genes? The “reduction hypothesis” suggests that this could have happened if parasitic cells rid themselves of most of their genes and became dependent on other cells.⁴ Researchers know that bacterial pathogens like sexually-transmitted Chlamydia trachomatis and typhus-causing Rickettsia prowazekii have purged genes important for synthesizing biomolecules because they can just sequester those resources from their hosts.⁸

Since all viral realms contain a portion of genes homologous to cellular proteins, it seems likely that viruses emerged in the same way as obligate intracellular pathogenic bacteria—by reduction of a cellular genome, but to a more extreme extent. The discovery of giant viruses in the realm Varidnavira originally lent support to this theory.⁹

“Giant viruses look like cells. They were confused with small bacteria at the beginning,” said Gustavo Caetano-Anollés, an evolutionary biologist at the University of Illinois Urbana-Champaign. Whereas most viruses contain hardly any genes (such as SARS-CoV-2, which caused the COVID-19 pandemic with merely 11 protein-coding genes), giant viruses carry thousands of genes.¹⁰ Many of them code for cellular factors like translation enzymes or ribosomal proteins, providing more evidence that they could have been reduced from cells.¹¹ “I think they’re a case for the reductionist hypothesis, actually, because maybe with a few more genes, they would become independent agents,” Zerbini said.

However, a study from 2023 challenged this view, finding that giant viruses probably emerged from smaller viruses instead.¹² Virologists used CRISPR-Cas9 to delete each gene from the giant Pandoravirus one by one to determine which ones were essential for its survival. They found that all the essential genes clustered together in the genome, whereas non-essential ones were appended on the ends. This suggested that the essential cluster represents a relic genome that was expanded later, said Hugo Bisio, a virologist at the French National Center for Scientific Research who coauthored the study. “In some cases, they create their own genes, and in others they steal genes from other organisms,” he said.

Giant viruses could have acquired genes by non-homologous end joining, whereby genes insert between two broken segments of DNA, or by homologous recombination, whereby genes with similar sequences swap places.¹³ There is no reason why these processes would happen at the ends of the essential cluster but not in the middle of it; however, Bisio speculated that the reason there only appear to be insertion events at the ends is because any insertion disrupting essential genes in the middle cluster would prevent the virus from replicating.

However, scientists remain split on how giant viruses emerged. Zerbini argued that acquiring genes from cells would seldom happen. “We assume that they are relatively rare events. So, for a virus to acquire hundreds of genes from hosts, that’s not impossible, but it’s very unlikely,” he said. Chantal Abergel, a virologist at the French National Center for Scientific Research who also coauthored the 2023 study noted, however, that “their lifecycle is so rapid that actually, on a small time scale, they will replicate so many times that eventually the chances to integrate new DNA is higher than for an organism that would replicate much slower,” like prokaryotes or eukaryotes.

Did Cell Components Escape to Become Viruses?

Genome reduction isn’t the only way that viruses could have emerged from cells. The “escape hypothesis” suggests that viruses could have emerged from a few cellular components that broke loose.⁴ Perhaps the most compelling evidence for this comes from the realm Riboviria, which contains retroviruses like human immunodeficiency virus (HIV). Retroviruses are RNA viruses that produce DNA copies of their genomes that they insert into host DNA. It is possible that these arose from retrotransposons, a type of “jumping gene” that inserts into the genome and duplicates.¹⁴

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In a study published this year, John O’Brien, an evolutionary virologist at the University of Oxford, and his colleagues mathematically modelled how the escape hypothesis could produce viruses.¹⁵ Their model predicts that viruses could have emerged if ancient cells divided unequally, allowing jumping genes or other self-replicating nucleic acids to break away from the genome. They tested out different rates of unequal division.

“What we found is that it does have to be happening commonly in order for viruses to arise via this method,” O’Brien said. “There should be a 50 percent chance every time a cell divides that there is an unequal cell division,” he added. “That is a critical part.” This may explain why most viral realms emerged near the dawn of life, when less robust cells with more fallible cell division dominated, he explained.

Though the escape hypothesis has garnered more support, some biologists believe multiple origin theories could apply to a single realm and have developed the “chimeric origin hypothesis,” which merges the escape and virus-first hypotheses.⁷ Bisio is fond of the hybrid theory, which assumes viruses evolved in a modular fashion, starting with replication machinery and then adding on capsid proteins later.

“What they propose is that this replication module originated very early, so before cells, and in fact, it was kind of evolving with the machinery that the cell has nowadays,” he said. For example, scientists think that primitive RNA polymerases from the RNA world gave rise to modern viral and cellular polymerases.^16,17 “The morphogenesis module arrived later, more in the way of the escape theory,” Bisio said. Some capsid components, like the “Swiss roll” protein fold that resembles the cake of the same name, have similar sequences to cellular proteins, suggesting the ancestral genes to capsids were captured from cellular genomes.⁷

Viruses Emerged More Times than Expected

Each viral realm may have originated in a different fashion. “In some cases, the evidence points towards the reduction hypothesis. In other cases, the evidence points more towards the escape hypothesis,” Zerbini said. As better sequencing data pour in, scientists are beginning to more accurately group viruses into evolutionary trees. Zerbini believes these organisms will be divided into more realms, indicating that viruses emerged more times than previously imagined and at different points in life’s chronology.

A DNA virus realm called Monodnaviria will most likely be split into four realms, following an initial vote by the ITCV in July this year, Zerbini said.³ The committee still needs to cast a second vote in November and a ratification vote in January 2026 before the new classification becomes official, but Zerbini believes the evidence to split Monodnaviria into four is persuasive. For example, one of the viral kingdoms in the realm, Shotokuviria, has DNA-cutting endonucleases and DNA-unzipping helicases that are also present in bacterial plasmids but missing in the other viruses of this realm, suggesting that this kingdom emerged independently by escape from bacteria, Zerbini said.

Monodnaviria isn’t the only realm undergoing a divide. “It’s very likely that Riboviria is going to be split into two realms” at a later stage, Zerbini said. This realm contains two kingdoms: one containing viruses that can reverse transcribe RNA into DNA, such as retroviruses, and one with viruses that encode RNA polymerases that use RNA strands as templates for replication, such as influenza.

“Most likely each kingdom is going to be upgraded to a realm,” Zerbini said. “For the reverse transcribing viruses, there is very strong evidence that they evolved from retrotransposons” because of overlap in their gene sequences, he added. As for the other kingdom, they probably evolved their RNA polymerase from ancient enzymes in the RNA world when RNA was the dominant biomolecule. “That’s why they infect viruses in all domains of life, because they evolved before cellular organisms evolved,” Zerbini added.

Splitting Monodnaviria or Riboviria could have huge implications on understanding their origins. Both realms infect all domains of life, suggesting they arose around the time of LUCA, but the new splits would rewrite their history. If Shotokurivia escaped from bacteria and reverse transcribing viruses escaped from retrotransposons inside cells, it suggests that they arose later on, long after cells took shape.

Understanding how viruses came to be could help scientists decode their elusive workings. “The main purpose of all this work will be to provide basic knowledge to better understand how the virus is replicating and what are the key factors for its efficiency,” Abergel said. A deep dive into virus origins could also elucidate how contemporary viruses evolve, O’Brien noted. Studying how historic viruses usurped cellular genes could help researchers understand how modern viral counterparts may do the same, he said.

As viruses were among some of the first entities on the planet, evolved in tandem with cells, and will continue to adapt, their origin stories still have much to tell researchers about life on Earth.