By Vidya Rajan, Columnist, The Times
Viruses are one of the greatest mysteries of biology. In fact, they are so problematic that some biologists do not consider that viruses are biological, relegating them instead to chemistry. Regardless of which camp one adheres to, viruses are significant to living organisms through their parasitism. Because of their obligate parasitism – they require living cells for reproduction – one of the most profound discoveries for genetic engineering, called CRISPR, was made on the back of viral infections of bacteria. CRISPR is a sort of immune system of bacteria, and it operated through recording historical infections by bacteriophages (bacteria-specific viruses) by inserting a part of the infecting virus into the genome. They behaved like a vaccination library. If another attack happened by the same virus, these sequences would be activated and mirror image copies of the viral genome made that would glom on specifically to the genome of the invading virus, thus inactivating it and preventing infection. But if viruses are not biological, why would a biological system like a bacterium care to produce an inheritable physical record for future generations to be protected from infections? And if viruses are chemicals, what is the nature of parasitic chemicals that replicate in a living cell?
Viruses typically contain either DNA or RNA as genetic information typically enclosed in a protein shell. Viruses infect all kindoms* of life, and some ‘satellite’ viruses even require other viruses for replication[1]. Viruses are tiny – they are on average 1/1000th the size of a bacterium, which is itself about 1/1000th the size of our body cells, which are themselves pretty small; so a virus is one millionth of the size of our body cells. Viruses can be crystallized and stood on a laboratory shelf for decades, only to become virulent when they are reconstituted and exposed to their host. They can be frozen in permafrost for 30,000 years and yet resurrect their infectivity when thawed. Each type of organism has viruses that are specialized to infect that host only. Occasionally a virus may jump from one host to another, such as happened with HIV, which moved from chimpanzees to humans, or influenza A which moved from birds to humans. Generally, plant viruses, termed viroids, are just naked loops of RNA, bacterial viruses have a protein outer shell, and animal viruses wear a coat made of cell membrane from the last cell they infected. Some viruses explode the cells they infect like the creature from the movie Alien; some tuck themselves in the genome for the long ride – quietly in some cases, noisily in others. A few of these long term residents, termed prophages, encode toxins which cause significant bacterial diseases. Examples are cholera toxin by the CTXj virus in the bacterium Vibrio cholerae, diphtheria toxin in Corynebacterium diphtheriae by phage b, and scarlet fever exotoxin encoded by virus T12 in Streptococcus pyogenes.[2] If you look inside your own cells right now, about 1/8th (12.5%) of “your” DNA is composed of viruses.[3] And yet, many biologists do not consider viruses to be biological agents. They consider viruses self-replicating chemicals – parasitic chemicals – which use the host’s energy to replicate. But this brings up the disconcerting thought: how can chemicals be parasites?
Consider what a delightful position this is for a scientist to be in. Naturally enough, from being curious, most scientists thrive in the realm of the unknown. They are excited by uncertainty, stimulated by what is yet to be learned. They poke around, each shining small pinpricks of light like fireflies, illuminating minute areas of knowledge in the hope that one day it will contribute to greater knowledge.
Let’s consider the knowledge already available about viruses. The Baltimore classification groups them into seven groups based on how they make their messenger RNA which is used for viral replication. The schema below provides a summary.
Figure 1: Baltimore classification of viruses based on mechanism of synthesis of mRNA prior to hijacking the host cell for replication, and examples.
On top of this, there are viroids (naked RNA circles which attack only plants), satellites (which require a host cell containing a different ‘helper’ virus which replicate normally); defective interfering particles (which need a helper virus, but can interfere with the helper virus’ own replication) and viriforms (which have incorporated themselves into the genome but may assist the owner with their infectivity and survival).
This is as good a time as any to run through the mechanisms by which viruses are thought to have evolved. There are three hypotheses.[4] In the Virus First Hypothesis, self-replicating chemicals coalesced and accrued more and more genomic material until they became the first cells. The second hypothesis is the Progressive Hypothesis, which posits that viruses evolved from mobile genetic elements in the genome. These typically contain transposons[5] (also referred to as jumping genes or mobile genetic elements) which typically move locations within a cell, but some move between cells. Retroviruses, such as HIV, are examples of such a mechanism. The human genome contains about 42% of retrotransposons, that could become such “retroviruses”.[6] The third hypothesis is the Regressive Hypothesis, which Chlamydia and Rickettsia seem to be heading towards, that of an intracellular bacterium which sheds more and still more of its genome, thereby becoming dependent on its host for replication, trending to becoming a virus. The reason this matters is that the origin of viruses is a mystery. It is not clear which if any, or all, of these hypotheses are correct.
Imagine, then, the excitement of a biologist watching a bacterium called Sukunaarchaeum which is in the process of shedding its genome so consistently that it is starting on the path to becoming a bag of parasitic chemicals.[7] Sukunaarchaeum is a parasite which lives inside the cells of its host, the protist dinoflagellate Citharistes regius. Dinoflagellates are tiny marine planktons which have symbiotic cyanobacteria to help them do photosynthesis. Some can also produce red tides which cause fish and shellfish kills due to the neurotoxins they produce. “Dino” means “terrible”, “flagellate” refers to the presence of mobility-assisting tail-like flagella, and dinoflagellates can cause serious harm! (Random useful information: Red tides happen in summer, and there is a handy saying for when to avoid shellfish in the northern hemisphere, because shellfish are filter-feeders, and concentrate these dinoflagellates in their bodies and can transmit the neurotoxin into humans when they are eaten – ‘Never eat shellfish in months which lack an ‘r’ – May, June, July, August’. Having said that, waters are warming due to climate warming, and dinoflagellate red tides are coming earlier and lasting longer, so be careful.) Sukunaarchaeum is oddly small: it has a mere 189 genes and a genome which is just 5% of the size of the familiar bacterium, E.coli; it also appears to be losing more of its genome, and reverting to an organism that leans into its host to help it replicate. Further, it seems to be an archaebacterium, not a bacterium. These two groups of prokaryotes (primitive organisms lacking a nucleus and cellular organelles) diverged as far back as 3.5 billion years ago, but they met and partnered up to make eukaryotes. It appears that one of the eukaryotes, a dinoflagellate, picked up this archaebacteria freeloader, who then started shedding its genes. Biologists are watching this space, but it seems like viruses can play it forward – spin out from cells as mobile genetic elements, or the reverse – enter cells as bacteria and then progressively diminish into bags of chemicals.
Finally, to the Virus First hypothesis. In nature there are giant viruses that are so enormous in size that they are sometimes termed girus (from giant virus). These viruses can be as big as bacteria and belong to the clades Mimivirus and Megavirus. Some of these giruses have genes for metabolism – that is, for making energy from food, which other viruses lack because they are not concerned with because they steal energy. Some giruses also have structural genes for cytoskeletal elements and the ability to make proteins from genes.
Life found a way. But it looks like viruses may have found three.
* I recently came across the word ‘kindom’ to describe what are typically referred to as ‘kingdoms’ of life – archaea, bacteria, protists, animals, fungi, and plants. Because of their common origin from a single progenitor, I am persuaded that kindoms better describes these groups than kingdoms, which are exclusionary. The word was used by mycologist Guiliana Furci in Robert Macfarlane’s masterly book, Is a River Alive?
References:
[1]. Krupovic, M., Kuhn, J.H. and Fischer, M.G. (2015). A classification system for virophages and satellite viruses. Archives of Virology, 161(1), pp.233–247. doi:https://doi.org/10.1007/s00705-015-2622-9.
[2] Kuhl, S., Hyman, P. and Abedon, S.T., 2012. Diseases caused by phages. Bacteriophages in health and disease, pp.21-32. PDF available at https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=bc6364de8a15eafb1cad41647851fa506084c5d2#page=38
[3]. ScienceDaily. (n.d.). Evolutionary surprise: Eight percent of human genetic material comes from a virus. [online] Available at: https://www.sciencedaily.com/releases/2010/01/100107103621.htm.
[4]. Wessner, D.R. (2010). Origin of Viruses | Learn Science at Scitable. [online] Nature.com. Available at: https://www.nature.com/scitable/topicpage/the-origins-of-viruses-14398218/.
[5]. Discovered by Barbara McClintock in 1946, for which she received the Nobel Prize in 1981. She discovered that multicolored Indian corn’s colors arose from such genes that happened to move into, and disrupt, pigment genes, giving rise to purple and white corn seeds on the same ear. See: Ulrika Royen (2025). BARBARA MCCLINTOCK – NobelPrize.org. [online] NobelPrize.org. Available at: https://www.nobelprize.org/stories/women-who-changed-science/barbara-mcclintock/.
[6]. Wessner, D.R. (2010). Origin of Viruses | Learn Science at Scitable. [online] Nature.com. Available at: https://www.nature.com/scitable/topicpage/the-origins-of-viruses-14398218/.
[7]. Microbe with bizarrely tiny genome may be evolving into a virus. (2025). AAAS Articles DO Group. [online] doi:https://doi.org/10.1126/science.z7ekqxv.
Vidya Rajan’s Rubber: The Social and Natural History of an Indispensable Substance (ISBN: 9789360455873) is now available on bookshop.org, bn.com, amazon.com, and other online retailers. Or ask for it at your local brick and mortar bookstore and at your public library. Read a review here and an interview here.
