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A new variant of the coronavirus has swept through the UK and has been detected in the US, Canada and elsewhere. Scientists fear that these new strains will not spread more easily.
As an evolutionary biologist, I study how mutation and selection combine to shape changes in populations over time. Never before have we had as much real-time evolutionary data as we do with SARS-CoV-2: more than 380,000 genomes were sequenced last year.
SARS-CoV-2 mutated as it spread, causing slight differences in its genome. These mutations allow scientists to trace who is linked to whom in the virus’ family tree.
Evolutionary biologists, including myself, have cautioned against overinterpreting the threat posed by mutations. Most mutations won’t help the virus, just as randomly kicking a working machine is unlikely to improve it.
But every now and then a mutation or a series of mutations gives the virus an advantage. The data is compelling that mutations carried by the variant that first appeared in the UK, known as B.1.1.7, make the virus ‘fitter’.
Better physical shape or luck?
When a new variant becomes common, scientists determine the reason for its spread. A virus carrying a particular mutation may increase in frequency by chance if it is:
- carried by a super-spreader;
- moved to a new, uninfected location;
- introduced into a new segment of the population.
These last two examples are called “founding events”: a rapid increase in frequency can occur if a particular variant is introduced into a new group and triggers a local epidemic. Fortuitous events may explain the increased frequency of several different variants of SARS-CoV-2.
But B.1.1.7 is an exception. This shows a very strong selection signal.
Over the past two months, the frequency of B.1.1.7 has increased faster than non-B.1.1.7 practically every week and every health region in England. The data, released on December 21, 2020, helped convince British Prime Minister Boris Johnson to place much of the country on lockdown and led to widespread travel bans in the UK.
The rise of B.1.1.7 cannot be explained by a founding event in new regions, as COVID-19 was already circulating across the UK.
Founding events in a new segment of the population (for example, following a conference) are also not plausible given the widespread restrictions against large gatherings at the time.
Our ability to follow the evolution of SARS-CoV-2 is due to the massive effort of scientists to share and analyze data in real time.
But the incredibly detailed knowledge we have on B.1.1.7 is also due to simple stupid luck.
One of his mutations altered a section of the genome used to test for COVID-19 in the UK, providing a picture of the evolutionary spread of more than 275,000 cases.
Evolution in action
Epidemiologists have concluded that B.1.1.7 is more transmissible, but there is no evidence that it is more fatal.
Some researchers estimate that B.1.1.7 increases the number of new cases caused by an infected individual (called the reproductive number or Rt) by 40 to 80%; another preliminary study found that Rt increased by 50 to 74%.
A 40 to 80% advantage means that B.1.1.7 is not only a little fitter, he is a lot fitter.
Even when the selection is so strong, the evolution is not instantaneous. Our mathematical modeling, along with that of others in Canada and the United States, shows that it takes a few months for B.1.1.7 to reach its meteoric rise, as only a small fraction of cases initially carry the new variant.
For many countries, like the United States and Canada, where the number of COVID-19 cases is precariously increasing, a variant that increases transmission by 40 to 80% threatens to push us over the top.
This could lead to an exponential growth in cases and overwhelm already exhausted medical care. Evolutionary change takes a while, perhaps buying us a few weeks to prepare.
More variations
A surprise to the researchers was that B.1.1.7 carries a remarkable number of new mutations.
B.1.1.7 has accumulated 30-35 changes in the past year. B.1.1.7 does not mutate at a higher rate, but appears to have undergone an episode of rapid change in the recent past.
The virus may have been carried by an immunocompromised person. People with weaker immune systems fight the virus all the time, with prolonged infections, recurring cycles of viral replication, and only a partial immune response to which the virus is constantly evolving.
(NextStrain / CC BY 4.0)
Above: Each dot represents a SARS-CoV-2 genome, with branches connecting related viruses to their ancestors. The center represents the virus introduced into humans. Viruses farther from the center carry more mutations. All three new variants are highlighted in gold.
Preliminary research reports that have not yet been verified have described two other variants of concern: one from South Africa (B.1.351) and the other from Brazil (P1).
Both variants show a recent history of excessive mutations and rapid increases in frequency within local populations. Scientists are currently gathering the data necessary to confirm that selection for higher transmission, and not chance, is responsible.
What has changed to allow propagation?
Selection plays two roles in the evolution of these variants.
First, consider the role within these individuals in which the large number of mutants arose. The 23 mutations of B.1.1.7 and the 21 mutations of P1 are not arranged randomly in the genome but grouped together in the gene encoding the spike protein.
A change in the peak, termed N501Y, occurred independently in all three variants, as well as in immunocompromised patients studied in the US and UK. Other changes in the peak (eg E484K, del69-70) are seen in two of the three variants.
Beyond the peak, the three worrisome variants share an additional mutation that removes a small part of the “non-structural protein 6” (NSP6) called drably.
We don’t yet know what the deletion does, but in a related coronavirus, NSP6 tricks a cellular defense system and can promote coronavirus infection.
NSP6 also hijacks this system to help copy the viral genome. Either way, removal could alter the ability of the virus to take hold and replicate in our cells.
Easier transmission
The parallel evolution of the same mutations in different countries and in different immunocompromised patients suggests that they convey a selective advantage in evading the immune system of the individuals in which the mutations have occurred. For N501Y, this was confirmed by experiments in mice.
But what explains the higher rate of transmission from one individual to another? This question is difficult to answer because the many mutations that occurred at once are now lumped into these variants, and it could be any one or a combination of them that leads to the advantage of inheritance. .
That said, several of these variants have appeared on their own before and have not led to rapid spread.
One study showed that N501Y had only a small inheritance advantage on its own, increasing rapidly only when coupled as a result of mutations seen in B.1.1.7.
While the evolutionary story of COVID is still being written, an important message is now emerging. The 40-80% transmission advantage of B.1.1.7, and potentially the other B.1.351 and P1 variants, will overwhelm many countries in the coming months.
We are in a race against viral evolution. We need to deploy vaccines as quickly as possible, stem the flow of variants by limiting interactions and movement, and deal with the spread by stepping up surveillance and contact tracing. 
Sarah Otto, Killam University Professor of Evolutionary Biology, University of British Columbia
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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