The pandemic allowed us to study the details of the evolution – in real time. Scientists have generated more than two million genomic sequences of the SARS-CoV-2 virus, which allows us to dissect the details of evolutionary changes to a degree never before possible for any biological agent replicating outside the laboratory.
So what does this tell us about mutations and variants? Mutations are the ultimate engine of evolution and provide the raw material for natural selection to work. Certain mutations are useful for an organism and can be generalized in the species. Others are harmful or have little impact. They occur due to errors when the genome is copied when a virus replicates, resulting in the replacement of only one “base” (letter) by another.
The SARS-CoV-2 genome is made up of 30,000 individual bases. The rate at which mutations occur is usually expressed as the likelihood that an individual base will be mistakenly replaced when the genome replicates. According to recent experimental evidence – which has not yet been published in a scientific journal – that figure is around three in a million.
Considering this rate, we may wonder how many mutations can occur each time a person is infected. By multiplying 30,000 bases with the probability of 3 / 1,000,000, we get a total of about 0.1 mutation for each genome replication.
The peak of infection lasts for five to seven days, during which time the virus typically goes through three to seven “replication cycles” (the stages from the initial attachment to a host cell to the generation and release of newly viral particles. synthesized). Five rounds of replication would result in about 0.5 mutations (5 × 0.1), or one new mutation for every two people infected.
A different approach is to use genome sequence data. Because each sequence in the genome comes from a different infected person, this data allows us to calculate the rate at which mutations have accumulated in the global viral population, rather than within a single infection. By comparing the sequence data to an original “reference” genome (a very early viral genome), we can count the number of accumulated mutations in each genome. We can then see how quickly the number of mutations increases over time.
This tells us that the global virus population accumulates on average about one mutation every two weeks – a rate similar to that of a single infected person.
To put this rate of mutation in context, human genomes undergo the equivalent of about 0.05 mutations every two weeks. At first glance, it’s not that different from SARS-CoV-2 (only 20 times slower), until you consider the human genome to be 100,000 times larger, which makes the mutation rate by base be about two million times faster in the virus than in humans.
Thus, SARS-Cov-2 experienced roughly the same amount of evolutionary mutational changes during the pandemic (proportional to genome size), as humans have since. Homo habilis first traveled the Earth about 2.5 million years ago.
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The calculation described above refers to the number of mutations expected within the same descendant line (lineage) from one viral particle to the next, and so on. To calculate the total number of mutations occurring during an infection, we also need to take into account all the viral particles produced, each following its own mutational path.
The total number of infectious viral particles produced during one infection is approximately 300,000 and 300,000,000. If each line accumulates an average of 0.5 mutations, then the estimate of the total number of mutations during one. an infection in all virus particles combined will be between 100,000 and 100,000,000 – which is conservative rather than correct.
The virus’s RNA code contains four letters: G, C, U and A – there are 30,000 in the genome. The mutation can change one of these letters to one of the other three letters of the code. This gives about 100,000 possible unique mutations in total.
It therefore follows that all possible unique mutations are likely to occur during each unique infection. So why haven’t we seen dangerous new variants emerge before several months of the pandemic?
The overwhelming majority of these mutations will not have significant consequences, or even be harmful to the virus. In addition, only a tiny fraction of the viral particles present in an infected person causes other infections. Almost any mutations that accumulate in a host will be lost after the infection resolves. In addition, since the time between infections is short, natural selection will have little opportunity to choose the “best” mutants with which to infect new hosts.
We should be extremely grateful for these narrow genetic “bottlenecks” as the virus is transmitted from host to host. It’s sobering that countless new dangerous variants may have emerged in infected people across the world, but aside from the half-dozen mutants lucky enough to transmit and subsequently spread to become worrying variants, they were quickly relegated to evolutionary oblivion.
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The fact that almost all the mutations occurring within the same infection never spread in the world confers a major evolutionary handicap on the virus. However, this can be compensated for if the total number of infections is very large.
At the time of writing, there are approximately 620,000 infections per day worldwide. If an infection transmits an average of 0.5 mutations, that means that overall, around 300,000 new mutations are passed from one host to another every day.
Just as the overwhelming majority of mutants occurring in a single infected person will never be transmitted, so the vast majority of those who do pass through an initial transmission event will not spread more widely in the population. But remember that the maximum number of possible mutations is around 100,000. It is therefore conceivable that each possible mutation of the viral genome is transmitted from one person to another every day.
This may give the impression, as some commentators have recently expressed, that the virus may be running out of scalable options and the risk of new dangerous types emerging is low.
However, some properties of the virus might not be determined by single mutations acting alone, but by the interaction of several mutations acting in concert on the same genome. For example, the effect of a specific mutation can be greatly enhanced if it occurs in a genome that has already been affected by other specific mutations. If such effects are common in SARS-CoV-2, then the virus may still have some evolutionary tips to draw from.
Ed Feil, Professor of Microbial Evolution at the Milner Center for Evolution, University of Bath
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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