Mutations Provide a Road Map to Taming Coronavirus

Mutations Provide a Road Map to Taming Coronavirus

By Ian Bott and Clive Cookson

Scientists are creating a vast genealogical tree that will be crucial to halting the pandemic and developing medicines.


Because a vaccine starts here.

By Ian Bott and Clive Cookson

Scientists studying mutations in the coronavirus have decoded more than 10,000 different genomes of the deadly pathogen, creating a comprehensive map that will be crucial to controlling the pandemic and developing medicines to treat it.

Since the first viral sample was analyzed in the Chinese city of Wuhan in December, international research teams have used phylogenetics to create a vast genealogical tree of the Sars-CoV-2 virus responsible for COVID-19, which reveals how it spread from the outbreak center to all corners of the world.

“Genomic epidemiology will be a vital tool in humanity’s efforts to beat COVID-19 and return the world to normal,” said Emma Hodcroft, an evolutionary geneticist at the University of Basel in Switzerland, who is part of the Nextstrain mapping project. “For a start, it will be instrumental for helping to distinguish between local and imported transmissions as we move out of lockdown.”

The genome analysis confirms that Europe and North America had no cases before mid-January.

The map of mutations will be used to understand any subsequent waves of the virus if and when the current outbreak can be brought under control, as well as the development of the drugs and vaccines that will allow that to happen. When these are finally introduced, the genome technology will be employed to detect any signs of a developing resistance. About 80 vaccines and 150 drugs for COVID-19 are being worked on around the world.

All viruses mutate and none of the changes in Sars-CoV-2 have altered its behavior or made it more dangerous — or not so far. The mutations could be as small as one of the roughly 30,000 biochemical letters that make up the virus. The biggest difference between genomes is currently 40 letters.

“People have talked about different strains evolving as the virus spreads and mutates, but we think it is dangerous to use that term because it suggests that the mutations are making the virus more or less transmissible or virulent,” said Hodcroft, whose collaboration has produced a series of spectacular graphics illustrating how the virus spreads. Scientists also share the results of their work through open databanks such as Gisaid. 

Like many viruses, Sars-CoV-2 stores its genes as RNA, the sister molecule to DNA. Because the viral genome evolves at a steady rate as it replicates, averaging about 2.5 mutations a month, scientists can use this as a molecular clock. The genetic difference between Sars-CoV-2 samples gives an accurate estimate of when the lineages separated from one another.

This technique allowed researchers to pin down when the virus began to circulate in China. “Late November is where our sequences are pointing — possibly mid-November but no earlier than that,” said Hodcroft.

This quashes the idea that the virus reached some Western countries last year and circulated in secret before the epidemic came to public attention. 

“There is a lot of Twitter chatter surrounding a rumor that circulation of COVID-19 in California in the fall of 2019 has resulted in herd immunity,” said Trevor Bedford, an associate member of the Fred Hutchinson Cancer Research Center in Seattle, who leads the Nextstrain project. “This is empirically not the case.” The genome analysis confirms that Europe and North America had no cases before mid-January.

Examples of the geographical diversity of COVID-19 introductions can be best seen in Iceland, which has carried out more testing and genomic analysis of Sars-CoV-2 than any other country per head of population.

Kari Stefansson, chief executive of deCode Genetics, an Icelandic genomics company, said this had revealed how the virus entered the country through travelers from a number of countries, including those returning from skiing holidays in the Alps in late February.

“We have found patterns of mutation characteristic of outbreaks all over the world,” he said. “We have representation from the Iranian outbreak, from the U.S. West Coast and around Europe, including a lot from the U.K.”

One aspect of Sars-CoV-2 is how it has evolved more slowly than some other viruses such as HIV or the flu. Just 40 differences have evolved so far between the most distantly related samples.

Although surveillance has not shown any mutations that would affect its transmissibility or virulence, scientists are watching closely in case they appear.

“As the epidemic progresses, some lineages will proliferate and others will go extinct,” said Nick Loman, a microbial genomics professor at the University of Birmingham.

“We could certainly have mutations that change the character of the virus,” he added, “though we have not yet seen this happening.”

By Ian Bott and Clive Cookson

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