The Extraordinary Evolution of Viruses

Figure 1: Colourised image of Ebola particles infecting the cell from a scanning electron microscope.
Credit: NIAID [CC BY 2.0] [1]

The word 'virus' traces directly back to the identical Latin word, meaning poison or venom. Thousands of years later, the word remains unchanged, but viruses themselves have evolved into something far more deadly than a simple poison. How is it that structures too tiny to be seen by most light microscopes can mutate so quickly against our genetic defences to destroy countless organisms? Darwin himself would marvel at the long and complex evolutionary history of viruses, and the way they manipulate the genetics of their hosts to keep them alive. Viruses are indeed evolution’s sneakiest poison – but is there any way to truly figure them out? Perhaps a breakthrough is imminent, or perhaps, by fully understanding what makes viruses special, we could use their intricacies to our advantage in other scientific fields.

Viruses: An Introduction

Figure 2: 3D representation of a spherical measles particle. Reprinted from Ref [3].

It could be said that viruses dance on the line between living and nonliving entities. Over the years, research into the structures and functions of viruses have no doubt been limited by our technology. Only when the electron microscope was developed in 1931 were the very first viruses seen under the microscope, an astonishing sight considering how much smaller they are than bacterial and human cells. The majority of viruses range in size from 5 - 300 nanometers, exceptions including later discovered giant viruses such as pandoraviruses [2]. Viruses are microscopic structures made up of a nucleic acid surrounded by a protein coat capsid, although the structure varies between species. The genetic material is either comprised of DNA, the double-stranded molecule with the nucleobases adenine, cytosine, thymine, and guanine, or out of RNA, the single-stranded, shorter molecule with uracil in place of thymine [4, 5]. The capsid is made of viral structural proteins coded for by the limited genome. Occasionally, viral species will have an extra envelope, partly taken from a membrane within its host [5]. 

Viruses cannot survive outside of a host cell, which is a key aspect to remember as we delve deeper into their evolution as one of humanity’s largest killers. Because of their limited genome, they rely on the host genome to help them replicate and survive. While viruses do not share most of the characteristics of living organisms, their ability to reproduce is uncannily like that of the rest of the living species on earth. They are not a part of the Tree of Life, and it is accepted that the Last Universal Common Ancestor of archaea, protists, bacteria, and fungi did not evolve into a virus [6]. So, where did these curious molecules come from, and what could they go on to be?

The Origins of Viruses

Viruses are simultaneously incredibly similar and tremendously different from the host species they inhabit. Several theories are currently circulating about where the very first virus emerged.

Figure 3: 3D representation of a double shielded Rotavirus viron. Reprinted from Ref [10].

One such theory is the progressive theory of viral evolution. This suggests that mobile genetic elements within already existing cells gained the ability to move out of their cell and infect others [7, 8, 9]. This theory is especially evident when looking at retroviruses (such as HIV), which share a remarkable resemblance to retrotransposons; these are a type of ‘jumping genes’ within cells. These retrotransposons can move sections of genes to a different location in the genome. This happens through the conversion of sections of DNA into RNA, similar to transcription in our cells, and then the conversion back to DNA using reverse transcriptase (a special enzyme). Scientists have observed the parallels between this process and the ability of retroviruses to insert their RNA into the host’s genome - this may mean retrotransposons evolved the ability to move out of the cell. These new elements, combined with the ability to infect, would be the early modern viruses.

While the progressive theory takes the approach that simpler elements evolved into the more complex viruses, the regressive hypothesis inverts this. The main concept of the regressive hypothesis is that viruses are less complex than their ancestors and lost many characteristics as they evolved. The evidence for this comes primarily from nucleocytoplasmic large DNA viruses (NCLDVs), which are large, intricate viruses composed of DNA. Mimiviruses, an example of these NCLDVs, are so complex that virologists have considered that the viruses we know now are simplified descendants of a larger organism [7, 8, 9]. According to this theory, a once symbiotic relationship between two separate organisms became parasitic. One organism became overly dependent on the other and lost its essential genes needed for replication and transcription. This now less complex organism was the ancestor of our modern viruses. Mimiviruses in particular may have traces of a genome this organism would have needed. Since this has been lost now, modern viruses must rely on their hosts’ genetic material.

Figure 4: High through-put Imaging Position Mapping shows the position of genes in a nucleus. Reprinted from Ref [11].

The virus-first hypothesis, in contrast, does not operate under the assumption that viruses evolved from cells. The first known molecules are believed to be self-replicating RNA molecules, bearing a remarkable similarity to current day viruses. If these original molecules evolved into more complex and able versions of themselves, viruses could have been the first biological molecules. The theory also suggests that these molecules could have sparked the beginning of eukaryotes. Eukaryotes are cells with a nucleus, such as plant and animal cells, as opposed to prokaryotes, which have free genetic elements rather than an enclosed nucleus. Endosymbiosis is a process in which one molecule envelopes another molecule, and the inner molecule becomes a permanent part of the outer one. With this understanding, viruses could have been engulfed by other molecules and become the framework for a nucleus inside a molecule, thus creating eukaryotes [7, 8, 9]. This would mean that viruses were present in our world long before any other molecule and a possible explanation as to why they are so adaptable to the evolution of their hosts.

Evolutionary Methods

Whichever way viruses first came into existence, one of their key characteristics is their ability to evolve quickly and efficiently to maximise their infection abilities. Their evolutionary methods provide a parallel with their hosts’, with slight differences. Furthermore, the evolutionary journey of a single virus is incredibly useful to study as it is a much quicker example of our own. Each new generation of viruses has a different genome, and those with the most beneficial genomes survive long enough to reproduce. Thus, creating several generations of viruses with the most effective genes. This is Darwin’s natural selection theory. The change in their genomes comes about in one of two ways: recombination or reassortment and mutation. Recombination can happen within the viruses’ genome, where sections of the genome cross over each other [12], or the virus can take a section of the genome from another carrier, most likely the host. If two strains of a virus co-infect a cell at the same time, the reassortment of the genomes can occur. This leads to a new strain of the virus being created, which is particularly relevant in the study of the influenza virus, and reinforces the need for regular new vaccines to fight these new strains [13]. Much like human genomes, viruses can also spontaneously mutate, and if these mutations are beneficial, natural selection will ensure that they are passed down to the virus progeny. Since RNA polymerases do not check the genes for mutations during replications as DNA polymerases do, mutations are more likely in RNA viruses than DNA viruses [14].

Unlike humans, however, viral evolution is a lot faster. The mutation rate of a virus’ genome is overall much higher than that of their host’s. Furthermore, the larger size of the virus population and shorter life cycle ensures that natural selection over generations works quicker in viruses than in other organisms. The high mutation rate causes the formation of the population structure known as a viral quasispecies - a variety of differently mutated genomes making up one viral species so that it is an average of different genetic sequences [15]. This is hypothesised to cause virus-virus competition, and the increased mutation rate involves viruses trying to become the strongest genome in that quasispecies [16]. 

Where is the evidence for viral evolution? We often refer to the fossil record in living organisms as proof that versions of an organism change over time, but viruses do not have any such physical fossil buried in rocks and sand. Instead, virologists turn to an interesting phenomenon in which viruses transcribe parts of their genome into their hosts’ in order to hijack host machinery into replicating the virus within cells [17]. This newly transcribed genome remains in the host and is passed down to generations of the hosts’ offspring. A shocking 8% of the human genome comes from traces of ancient, dead, viruses (endogenous viral elements) that once infected our ancestors and inscribed their genome [18].

Viruses and Human Evolution

Figure 5: Colourised image of a Middle east respiratory syndrome (MERS-CoV) viron from a transmission electron microscope (TEM). Reprinted from Ref [21].

The entanglement between viruses and animals is a long and complicated one. Not only do viruses evolve similarly to their hosts, but they also act as a major kind of selective pressure for many species, which is one of the drivers of natural selection. It was estimated, in a 2016 study, that viruses were responsible for 30% of changes to the amino acids in the human proteome (the total sequences of proteins in the body) [19, 20]. Some proteins in the human body are directly responsible for antiviral protocols within our cells. For example, protein kinase R (PKR) is able to recognise double-stranded viral RNA, and halt its translation, stopping the virus from using our cells to replicate [20]. However, there are many other proteins within the human body that interact with viruses. Studies involving these virus interacting proteins (VIPs) show that while they evolve overall more slowly than other proteins, their adaptation rate is higher [20]. It is clear that viruses have a huge effect on human evolution, whether having progressed to a pandemic level threat or not. Once more, we are reminded of the endogenous viral elements in our genome, which evidently have been a persistent trigger in many of our species’ evolutionary changes. 

Viruses in Today’s World

Figure 6: Preparation for a whole genome sequencing of a virus in the National Cancer Institute. Reprinted from Ref [23].

Smallpox, HIV, COVID-19. Chances are anyone you ask will either be familiar with or will have been infected by a common virus. In fact, each human being possesses their own set of viruses in their body at any one time, the human virome. This includes endogenous viral elements [22] as well as asymptomatic viruses which will not affect someone’s physical health. Deep sequencing involves technology reading the nucleotides in a genome, and is a chief technique in discovering novel viruses.

However, out of the billions of viral species known to exist, only a minute proportion has been found to infect humans and other animals. These do an efficient job, constantly mutating so fast that even the flu vaccine has to be redeveloped each flu season. Are we fighting a losing battle against viruses? It seems like we are, especially in the uncertainty of the pandemic we are living through. Having said that, remember that at one time influenza was a deadly and fatal disease instead of a common occurrence each winter. HIV is still a complex and worrying condition, but antiretroviral drugs are able to alleviate the fatal symptoms of AIDS, and many of those afflicted can live close to normal lives.

Progress in understanding viruses and their evolution has allowed scientists to tackle common viruses and begin to work on ways to dismantle their genetic abilities, but why is this so interesting? The answer lies in the curious nature of viruses that we have discussed. While dangerously efficient, the ‘life’ of a virus relies majorly on one thing: its host.

Figure 7: Results of a plaque assay to count how many virons are in a mixture. Reprinted from Ref [24].

The quicker a virus begins to kill off its host population, the closer it gets to death itself, and so the solution is to reach a point of equilibrium in which the virus only infects at a rate to keep the host population and itself completely alive [25]. This strange balance between infection and dependence raises many questions about how to fight viruses. Will we ever be able to completely get rid of them? Is the ideal world one in which viruses and hosts live in harmony? Is the sometimes fatal evolution of viruses actually beneficial to our biological systems? There are already treatments involving viruses themselves, for example, phage therapy. Bacteriophages are a specific type of virus, which target and infect bacterial cells, and have been used to fight bacterial infection [26]. In this age of antibiotics and drug resistance, viruses could be very useful in fighting diseases rather than causing them. Any developments in tackling viruses must take into account that viruses are likely to evade any attack we throw at them - unless we look to the beginning, the process of viral evolution, and solve from there.

Perhaps we never beat viruses. However, there is so much more about their nature to explore, so much so that in future eras they may become part of the research into other diseases and treatments. The parallels between the evolution of a virus and the evolution of a host are key to our understanding of these incredible structures, and possibly one day to us catching up with viruses before they catch up with us.

References

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