But sequencing data suggest that coronaviruses change more slowly than most other RNA viruses, probably because of a ‘proofreading’ enzyme that corrects potentially fatal copying mistakes. A typical SARS-CoV-2 virus accumulates only two single-letter mutations per month in its genome — a rate of change about half that of influenza and one-quarter that of HIV, says Emma Hodcroft, a molecular epidemiologist at the University of Basel, Switzerland.
Other genome data have emphasized this stability — more than 90,000 isolates have been sequenced and made public (see
www.gisaid.org). Two SARS-CoV-2 viruses collected from anywhere in the world differ by an average of just 10 RNA letters out of 29,903, says Lucy Van Dorp, a computational geneticist at University College London, who is tracking the differences for signs that they confer an evolutionary advantage.
Despite the virus’s sluggish mutation rate, researchers have catalogued more than 12,000 mutations in SARS-CoV-2 genomes. But scientists can spot mutations faster than they can make sense of them. Many mutations will have no consequence for the virus’s ability to spread or cause disease, because they do not alter the shape of a protein, whereas those mutations that do change proteins are more likely to harm the virus than improve it (see ‘A catalogue of coronavirus mutations’). “It’s much easier to break something than it is to fix it,” says Hodcroft, who is part of
Nextstrain, an effort to analyse SARS-CoV-2 genomes in real time.
...
The clearest sign that D614G has an effect on the spread of SARS-CoV-2 in humans comes from an ambitious UK effort called the COVID-19 Genomics UK Consortium, which has analysed genomes of around 25,000 viral samples. From these data, researchers have identified more than 1,300 instances in which a virus entered the United Kingdom and spread, including examples of D- and G-type viruses.
A team led by Andrew Rambaut, an evolutionary biologist at the University of Edinburgh, UK, epidemiologist Erik Volz, at Imperial College London, and biologist Thomas Connor at Cardiff University, studied the UK spread of 62 COVID-19 clusters seeded by D viruses and 245 by G viruses
7. The researchers found no clinical differences in people infected with either virus. However, G viruses tended to transmit slightly faster than lineages that didn’t carry the change, and formed larger clusters of infections. Their estimates of the difference in transmission rates hover around 20%, Volz says, but the true value could be a bit higher or lower. “There’s not a large effect in absolute terms,” says Rambaut.
It’s possible that D614G is an adaptation that helps the virus to infect cells or compete with viruses that don’t carry the change, while altering little about how SARS-CoV-2 spreads between people or through a population, Rambaut says. “This might be a bona fide adaptation to humans or some human cells,” agrees Grubaugh, “but that doesn’t mean anything changes. An adaptation doesn’t have to make it more transmissible.”
Grubaugh thinks that D614G has received too much attention from scientists, in part because of the high-profile papers it has garnered. “Scientists have this crazy fascination with these mutations,” he says. But he also sees D614G as a way to learn about a virus that doesn’t have much in the way of genetic diversity. “The virologist in me looks at these things and says it would be a lot of fun to study,” he says. “It creates this whole rabbit hole of different things you can go into.”
