Bath Chronicle

Covid’s mutation rate ‘50pc higher than was thought’

- Zasha Whiteway-wilkinson zasha.whitewaywi­lkinson@reachplc.com

Scientists at the universiti­es of Bath and Edinburgh have released a new study reporting that the mutation rate of Covid-19 is “at least 50 per cent higher than previously thought”.

The report says that the virus that causes Covid-19 mutates almost once a week, which is significan­tly higher than the rate estimated previously.

This means that the results indicated that new variants could emerge more quickly than initially thought.

The University of Bath say that the findings, published in the Genome Biology and Evolution journal, reinforce the need to isolate individual­s with immune systems that struggle to contain the virus.

They said: “SARS-COV-2, the virus that causes Covid-19, was previously thought to mutate about once every two weeks.

“However, new research from the Milner Centre for Evolution at the University of Bath and the MRC Human Genetics Unit at Edinburgh University, shows that this estimate overlooked many mutations that happened but were never sequenced.

“Viruses regularly mutate, for example when mistakes are made in copying the genomes whilst the virus replicates.

“Usually when we consider natural selection, we think about new mutations that have an advantage and so spread, such as the Alpha and Delta variants of Covid-19.

“This is known as Darwinian selection or positive selection.

“However, most mutations are harmful to the virus and reduce its chances of surviving - this is called purifying or negative selection.

“These negative mutations don’t survive in the patient long enough to be sequenced and so are missing from calculatio­ns of the mutation rate.

“Allowing for these missing mutations, the team estimates that the true mutation rate of the virus is at least 50 per cent higher than previously thought.”

Professor Laurence Hurst, of the Milner Centre for Evolution, said: “Our findings mean that if a patient suffers Covid-19 for more than a few weeks, the virus could evolve which could potentiall­y lead to new variants.

“The Alpha variant is thought to be the result of evolution of the virus within an individual who was unable to clear the infection.

“It’s not all bad news because most individual­s transmit and clear the virus before it mutates all that much, meaning that the chance of evolution within one patient isn’t usually that high.

“However, this new estimate of the mutation rate indicates that there is more scope for evolution of the virus within such individual­s than we assumed.”

The University of Bath also said that the “team could also work out why these mutations were missing”.

Prof Hurst said: “With the great number of genomes of SARSCOV-2 now sequenced we can say something about both how many and why these mutations are missing, despite the fact that we can’t fully study them directly.

“In the Second World War the Americans were losing lots of planes flying over Germany.

“They wanted to work out where they should add bulletproo­f material.

“They looked to see where the returning planes were damaged, reasoning that the locations without bullet holes in the surviving planes were those most vulnerable - shots to these places caused the plane to crash and hence not be seen in the returning planes.

“We can use the same sort of trick to work out the profile of the missing mutations in SARSCOV-2 : the sequenced genomes are the returning planes.

“We can work out both the proportion of all planes that return when shot by mutation and why some don’t return.

“Much of the negative selection they found was for predictabl­e reasons: the mutations make the genes shorter or they make the proteins, like the spike, function poorly. Other mutations, however, were a surprise.”

Lead author Dr Atahualpa Castillo Morales said: “The proteins that the virus makes are made up of amino acids.

“Like our genes, the virus’s genes have the instructio­ns as to which amino acids to glue together and in what order.

“Intriguing­ly, we found that selection favoured mutations that used amino acids which are more stable, meaning they don’t have to be made so often and it doesn’t cost as much energy to maintain supplies.

“We think we are seeing this because the virus is under strong selective pressure to replicate fast and so using amino acids with a longer shelf-life means you’re less likely to have to wait for supplies.”

The study was funded by the Wellcome Trust and European Research Council.

Our findings mean that if a patient suffers Covid-19 for more than a few weeks, the virus could evolve which could potentiall­y lead to new variants. It’s not all bad news because most individual­s transmit and clear the virus before it mutates.

Professor Laurence Hurst

 ?? Image: Davian Ho/innovative Genomics Institute ?? Around 40 per cent of mutations of the SARS-COV-2 virus reduce the virus’ ability to survive and so are not found in sequencing of samples from patients
Image: Davian Ho/innovative Genomics Institute Around 40 per cent of mutations of the SARS-COV-2 virus reduce the virus’ ability to survive and so are not found in sequencing of samples from patients

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