A new variant of coronavirus has spread to the United Kingdom and has been detected in the United States, Canada, and elsewhere. Scientists are concerned that these new strains may spread more easily.
As an evolutionary biologist, I study how mutation and selection combine to shape population changes over time. Never before had we had as much real-time data on evolution as we do with SARS-CoV-2: last year more than 380,000 genomes were sequenced.
SARS-CoV-2 has been mutating as it spreads, generating slight differences in its genome. These mutations allow scientists to track who is related to who in the virus’s family tree.
Evolutionary biologists, myself included, have warned about the over-interpretation of the threat posed by mutations. Most mutations will not help the virus, just as it is unlikely that random stitches on a running machine will be better.
But from time to time a mutation or set of mutations gives the virus an advantage. The data are convincing that mutations in the variant that first appeared in the UK, known as B.1.1.7, make the virus more “fit”.
A fitness or a higher opportunity?
When a new variant becomes common, scientists determine the reason for its spread. A virus that carries a particular mutation can increase in frequency by chance if it is:
- carried by a supercar;
- moved to a new uninfected location;
- introduced in 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 a local epidemic begins. Accidental events may explain the increased frequency of several SARS-CoV-2 variants.
But B.1.1.7 is an exception. Shows a very strong selection signal.
Over the past two months, B.1.1.7 has increased in frequency more rapidly than B.1.1.7 in virtually every week and health region in England. These data, published on December 21, 2020, helped convince the Prime Minister of the United Kingdom, Boris Johnson, to place much of the country closed and led to general bans on travel from the United Kingdom.
The increase in B.1.1.7 cannot be explained by a founding event in new regions, because COVID-19 was already circulating in the UK.
Founding events in a new segment of the population (e.g., after a conference) are also not plausible given the widespread restrictions against large gatherings at that time.
Our ability to track 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 about B.1.1.7 is also due to mere luck.
One of its mutations altered a section of the genome used to test COVID-19 in the UK, which allowed the image of the evolutionary spread of more than 275,000 cases to be removed.
Evolution in action
Epidemiologists have concluded that B.1.1.7 is more transmissible, but there is no evidence that it is more lethal.
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 percent; another preliminary study found that Rt increased by 50-74 percent.
A 40-80 percent advantage means that B.1.1.7 is not only a little tighter, but much tighter.
Even when the selection is so strong, the evolution is not instantaneous. Our mathematical modeling, as well as that performed by other countries in Canada and the United States, shows that it takes B.1.1.7 a couple of months to reach its meteoric rise, because only a small fraction of cases initially involve the new variant.
For many countries, such as the United States and Canada, where the number of COVID-19 cases has been precariously increasing, a variant that increases transmission by 40 to 80 percent threatens to overwhelm us.
It could lead to exponential growth in cases and overwhelm the already discouraging medical attention. Evolutionary change takes time and can take us a few weeks to prepare.
More variants
A surprise for the researchers was that B.1.1.7 has a remarkable number of new mutations.
B.1.1.7 has accumulated between 30 and 35 changes over the last year. B.1.1.7 does not mutate at a higher rate, but it seems to have experienced a rapid change in the recent past.
The virus may have been carried by an immunocompromised individual. People with weaker immune systems fight the virus constantly, with prolonged infections, recurrent viral replication wheels, 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 viruses related to their ancestors. The center represents the virus introduced into humans. Viruses farthest from the center carry more mutations. The three new variants stand out in gold.
Preliminary research reports that have not yet been verified have described two other worrying variants: one from South Africa (B.1.351) and one from Brazil (P1).
Both variants show a recent history of excess mutations and rapid increases in frequency in local populations. Scientists are currently collecting the necessary data to confirm that selection for superior, non-random transmission is responsible.
What has changed to allow dissemination?
Selection has 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 B.1.1.7 mutations and the 21 P1 mutations are not randomly distributed throughout the genome, but are grouped in the gene encoding the ear protein.
A change in the rise, called N501Y, arose independently in all three variants, as well as in immunocompromised patients studied in the US and the UK. Other changes in the rise (e.g. E484K, del69-70) are seen in two of the three variants.
Beyond the rise, the three variants of concern share an additional mutation that removes a small portion of the nonstructural protein 6 (NSP6).
We still don’t know what suppression does, but in a related coronavirus NSP6 tricks a cell defense system and can promote coronavirus infection.
NSP6 also hijacks this system to help copy the viral genome. Either way, suppression can alter the ability of the virus to catch 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 transmit a selective advantage to elude the immune system of the individuals in whom the mutations occurred. For N501Y, this has been supported by experiments in mice.
But what explains the higher rate of person-to-person transmission? This is difficult to answer, as the many mutations that arose at once are combined in these variants, and it may be any or a combination of them that leads to the advantage of transmission.
That said, several of these variants have already appeared on their own and have not caused a rapid spread.
One study showed that N501Y only had a weak transmission advantage, increasing rapidly only when combined with the set of mutations observed in B.1.1.7.
While the evolutionary history of COVID is still being written, an important message now appears. The transmission advantage between 40 and 80 percent of B.1.1.7, and potentially the other variants B.1.351 and P1, 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, curb the flow of variants by restricting interactions and displacements, and anticipate spread by increasing surveillance and contact tracking. 
Sarah Otto, Professor of Evolutionary Biology at Killam University, University of British Columbia
This article is republished from The Conversation under a Creative Commons license. Read the original article.