A new variant of the coronavirus has spread across the UK 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 changes in populations over time. Never before have we had as much real-time data on evolution as we have with SARS-CoV-2: more than 380,000 genomes were sequenced last year.
SARS-CoV-2 mutates as it spreads, generating small differences in its genome. These mutations allow scientists to track who is related to whom in the virus’s family tree.
Evolutionary biologists, including myself, have warned against over-interpreting the threat posed by mutations. Most mutations will not help the virus, just as randomly kicking a working machine is unlikely to do it better.
But every now and then a mutation or set of mutations gives the virus an advantage. The data is convincing that mutations carried by the variant that first appeared in the UK, known as B.1.1.7, make the virus more “suitable”.
Greater fitness or chance?
When a new variant becomes common, scientists determine the reason behind its spread. A virus that carries a specific mutation can increase in frequency by chance if it is:
- transported by a super spreader;
- moved to a new, uninfected site;
- introduced into a new segment of the population.
The 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 starts a local epidemic. Fortuitous events may explain the increase in the frequency of several different variants of SARS-CoV-2.
But B.1.1.7 is an exception. Shows a very strong check signal.
In the past two months, B.1.1.7 has increased in frequency faster than non-B.1.1.7 in virtually every week and in the health region of England. These data, reported on December 21, 2020, helped to convince UK Prime Minister Boris Johnson to place much of the country under confinement and led to the widespread travel ban in the UK.
The rise of B.1.1.7 cannot be explained by a founding event in new regions, because COVID-19 was already circulating throughout the United Kingdom.
Founding events in a new segment of the population (for example, after a conference) are also not plausible, given the widespread restrictions against large meetings at the time.
Our ability to track the evolution of SARS-CoV-2 is due to the enormous 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 sheer luck.
One of its mutations altered a section of the genome used to test COVID-19 in the United Kingdom, allowing the framework for evolutionary dissemination to be drawn in more than 275,000 cases.
Evolution in action
Epidemiologists have concluded that B.1.1.7 is more transmissible, but there are no signs that it is more deadly.
Some researchers estimate that B.1.1.7 increases the number of new cases caused by an infected individual (called 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 more suitable, it is much more suitable.
Even when the selection is so strong, the evolution is not instantaneous. Our mathematical modeling, as well as that of others in Canada and the United States, shows that B.1.1.7 takes a few months to reach its meteoric rise, because only a small fraction of the cases initially carry the new variant.
For many countries, such as the United States and Canada, where the number of COVID-19 cases has increased precariously, a variant that increases transmission by 40-80 percent threatens to push us to the top.
This could lead to an exponential growth of cases and overburden the already worn out medical care. Evolutionary change takes a while, perhaps giving us a few weeks to prepare.
More variants
A surprise for the researchers was that B.1.1.7 carries a notable number of new mutations.
B.1.1.7 accumulated 30-35 changes in the past year. B.1.1.7 does not mutate at a higher rate, but it appears to have experienced an outbreak of 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 rounds of viral replication and only a partial immune response to which the virus is constantly evolving.
(NextStrain / CC BY 4.0)
Above: Each point represents a SARS-CoV-2 genome, with branches connecting viruses related to their ancestors. The center represents the virus introduced into humans. Viruses further away from the center carry more mutations. Highlighted in gold are the three new variants.
Preliminary research reports that have yet to be verified describe 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 gathering the data needed to confirm that selecting for higher transmission, not chance, is responsible.
What has changed to allow it to spread?
Selection plays two roles in the evolution of these variants.
First, consider the role within those individuals in whom the large number of mutants emerged. Mutations 23 of B.1.1.7 and mutations of P1 21 are not randomly arranged in the genome, but grouped in the gene encoding the spike protein.
A change in the peak, called N501Y, appeared independently in all three variants, as well as in immunocompromised patients studied in the USA and the UK. Other changes in the peak (eg, E484K, del69-70) are seen in two of the three variants.
In addition to the peak, the three concern variants share an additional mutation that excludes a small part of the drably called “non-structural protein 6” (NSP6).
We still don’t know what the deletion does, but in a related coronavirus, NSP6 bypasses a cellular defense system and can promote coronavirus infection.
NSP6 also hijacks this system to help copy the viral genome. Either way, exclusion can alter the virus’s ability to establish itself 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 in escaping the immune system of the individuals in whom the mutations occurred. For the N501Y, this was supported by experiments on mice.
But what explains the higher rate of transmission from individual to individual? It is a challenge to answer because the many mutations that arose at the same time are now grouped in these variants and it can be any one or a combination of them that leads to the transmission advantage.
That said, several of these variants have emerged on their own before and have not led to rapid spread.
One study showed that N501Y had only one advantage of weak transmission on its own, increasing rapidly only when coupled with the set of mutations seen in B.1.1.7.
While the evolutionary history of COVID is still being written, an important message is now emerging. The 40-80 percent transmission advantage of B.1.1.7, and potentially the other B.1.351 and P1 variants, will dominate many countries in the coming months.
We are in a race against viral evolution. We must launch vaccines as soon as possible, contain the flow of variants, restrict interactions and travel, and prevent spread by increasing surveillance and contact tracking. 
Sarah Otto, professor of evolutionary biology at Killam University, University of British Columbia
This article was republished from The Conversation under a Creative Commons license. Read the original article.