Genetic mutation is an evolutionary fact of life. From humans to insects, and from bacteria to viruses, these coding corruptions can pop up anywhere and bring about a series of changes to an organism.
Cancer is one of the more better known outcomes of genetic mutation. Random errors that appear in the DNA of a cell can, every now and again, trigger a series of reactions that result in pandemonium: cellular dysfunction, rapid and uncontrolled growth, or the switching-off of a cell’s ability to spot and repair mutations.
All of these mutations fuel the proliferation of cancerous cells in an organism, sometimes culminating in death.
So what about viruses and, in particular, Sars-CoV-2?
There’s much debate and division within the scientific community as to whether viruses should be considered “alive”.
At a basic level, viruses are proteins and genetic material that survive and replicate within another life form. In the absence of their host, viruses are unable to replicate, and many are unable to survive for long in the extracellular environment.
In this sense, viruses are quite unlike any living organism in how they reproduce, depending exclusively on other organisms to stay “alive”.
The genetic material that makes up a virus can be either DNA or RNA – both of which are capable of storing and expressing information. Indeed, every protein ever synthesised within your body will have been shaped and designed by this nano-sized material.
The structural attributes of DNA and RNA account for one of the most crucial differences among viruses: the rate of mutation.
DNA is far more solid and robust thanks to its famed double helix: two strands entwined together in harmony, bound by very specific relationships between pairs of nucleotide bases. Remember these from school? A, C, G, T, U – think of these as the building blocks of life.
Should these bases ever be mismatched together during the construction of new DNA, an enzyme called polymerase springs into action to correct the mistake. This means, then, that the rates of mutation in DNA-based viruses – such as herpesviruses and poxviruses – are fairly low.
The same law of order doesn’t apply to RNA viruses, which are instead coded by a single chain of nucleotide bases, wrapped up and folded on to itself in a messy configuration that lacks the stability of DNA. There is no self-corrective arrangement or proofreading system propped up by the polymerase enzyme.
As a result, RNA viruses – such as the coronaviruses – sustain rates of mutation that may be thousands of times higher than their genetic cousins, making them far more volatile and unpredictable.
So what do these mutations mean? Many of the genetic corruptions are just that: irrelevant miscoding that serves no purpose or use for the virus, bringing it to an evolutionary dead end.
But when a virus becomes widespread in a population, this increases its chances of stumbling across a mutation that is actually of some benefit to the virus.
When this eventually happens, the mechanics of natural selection begin to whir, at which point this new, mutated, “improved” variant of the virus is fast-tracked to the front of the queue and given the opportunity to infect hosts at quicker rate, replicate in a shorter period of time or evade an immune response.
That is ultimately what we’re seeing with Sars-CoV-2. As more and more people become infected with the pathogen, probability tells us that mutations will crop up here and there on a regular basis.
Compared with other viruses out there, Sars-CoV-2 is deemed to be evolving relatively slowly, acquiring between one and two new mutations every month.
Even so, this means there could be hundreds of variants that have developed a whole host of mutations since the virus first emerged in China towards the end of 2019.
Scientists trace these variants through different lineages and sub-branches, enabling them to follow their evolution through regular mutation cycles.
Which brings us to B.1.1.7, the UK variant that has sparked so much global concern.
It harbours 23 mutations in total, six of which are “silent” and don’t have any function but “crop up and come along for the ride,” said Dr Jeffrey Barrett, lead Covid-19 statistical geneticist at the Wellcome Sanger Institute.
Others are significant and change the biology of Sars-CoV-2, altering the sequence and shape of certain proteins that make up the virus.
One of these mutations, known as N501Y, sits in the so-called “spike” protein – the part of the virus that is responsible for binding to human cells.
The mutation, according to the scientists, has increased the ability of the spike receptor to attach to certain proteins that cover our own cells, therefore making the virus more infectious.
A second notable mutation, named 69-70del, leads to the loss of two amino acids in the spike protein and the evasion of the immune response in some immunocompromised patients, evidence shows.
Both mutations have already been detected in other lineages of Sars-CoV-2 across the world, including the South African variant.
“These mutations haven’t just suddenly appeared out of thin air in the UK,” Dr Julian Tang, a virologist at the University of Leicester, told The Independent. “The individual mutations were circulating separately, globally, for some time before combining.”
He said that the two mutations on their own weren’t too problematic, but appeared to have “combined to make up this latest ‘fast spreading’ variant”.
Dr Tang explained that the N501Y mutation has been circulating in different forms of Sars-CoV-2 since April, while 69/70del has been detectable as far back as last January in cases in Thailand and Germany.
But while analysis has shown that the Covid-19 vaccines produce an immune response which is still capable of neutralising B.1.1.7, questions remain over whether this will be the case for the South African (501Y.V2) and Brazilian (P.1) variants.
Both share the N501Y mutation, along with a host of others – including E484K, which also affects the shape of the Sars-CoV-2 spike protein, but in a way that makes it less recognisable to the immune system.
For those people who have been infected with or vaccinated against a different variant of Sars-CoV-2, there’s a chance that both 501Y.V2 and P.1 could evade certain antibodies generated by the body’s immune response.
Professor Francois Balloux, a computational biologist at the University College London, said: “The E484K mutation has been shown to reduce antibody recognition. As such, it helps the virus SARS-CoV-2 to bypass immune protection provided by prior infection or vaccination.”
In addition, P.1 has acquired a curious, less well-studied mutation called K417T – the ramifications of which are still being researched. Could it make the virus even more transmissible? Could it heighten its ability to hide from antibodies and T-cells? At this stage, it remains unknown.
Ravi Gupta, professor of microbiology at the University of Cambridge, said: “The Brazilian variant has three key mutations in the spike receptor binding domain (RBD) that largely mirror some of the mutations we are worried about it in the South African variant, hence the concern.
“The Sars-CoV-2 RBD is one of the main targets for our immune defences and also the region targeted by vaccines, and changes within this region are therefore worrisome. Vaccines are still likely to be effective as a control measure if coverage rates are high and transmission is limited as far as possible.”
However, in spite of all these different mutations to the spike protein, scientists have insisted there are many other components to its structure that will still be recognised and neutralised by our immune systems.
And in the worst-case scenario, thanks to the new mRNA technology used to design many of our vaccines, it will take a matter of weeks to tweak and adapt these tools to overcome the new variants that are beginning to proliferate throughout the global population.
For now, it’s a case of waiting to see what the science says.