Like any other biological entity, SARS-CoV-2 has a family tree. It isn’t a very old one – the virus has only been recognised since December – but it still has tales to tell.
Most of what we know about this coronavirus comes from genetic analysis. The first complete SARS-CoV-2 genome sequence was read from a patient who worked at a seafood market in the Chinese city of Wuhan, and who was admitted to hospital on 26 December 2019 with symptoms of what turned out to be a new disease. Known as , it is a bit like the type specimen of a species – the reference against which all others are compared.
The sequence showed that the new disease was caused by a novel coronavirus closely related to a group found in bats. That was both good news and bad news. Coronaviruses are RNA viruses, which generally have the highest mutation rates of any known biological entity. RNA viruses are slippery customers, mutating often and hence evading drugs and immune defences. But most coronaviruses are an exception because their RNA-copying enzyme has a proofreading function. The assumption was that the new coronavirus would follow that rule and rarely mutate. But nobody knew.
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Tens of thousands of genomes from all over the world have since been sequenced, and are constantly slotted into an ever-growing family tree by the pathogen-tracking project at Fred Hutchinson Cancer Research Center in Seattle.
At first all was quiet. Sequences seen in China in December and early January proved identical to the reference. So were the first sequences from outside China – three in Thailand and one in Nepal – that were analysed in early January.
Then mutants started to appear. The first was collected in the Chinese province of Yunnan on 17 January. An identical one popped up in the US two days later. These were only two mutations away from the reference case, but in virology that is enough for them to be considered a new lineage.
Lineages, however, aren’t necessarily biologically different. That proved to be the case with this new lineage, which had no reported differences in infectivity or virulence.
The new lineage began circulating in Asia and was soon common enough to be classed as a “clade”, which is a lineage that accounts for at least 20 per cent of cases within its branch of the family tree. As more samples were sequenced, it became clear that this new clade had actually appeared in late 2019 so it was given the name 19B, to distinguish it from the original 19A clade.
For the rest of 2019 and the first few weeks of 2020, these two clades – 19A and 19B – stood alone. They circulated in Asia and cropped up sporadically in North America, Europe and Australia.
In late January a new lineage appeared in Australia and Europe. It was four mutations away from the reference genome, though again it didn’t appear to be biologically different. This lineage soon attained clade status, 20A, and dominated the European outbreaks of early 2020. It has since diverged into two other clades: 20B, which appeared in Europe, and 20C, a predominantly North American clade.
That, for now, is where we stand. All five clades constantly spawn new lineages but none is yet common enough to become a clade. All are found worldwide, though 19A remains largely confined to Asia. At some point a new clade will emerge – 20D if it happens this year or 21A if next.
This is a lower rate of divergence than might have been expected. by a team at the Walter Reed Army Institute of Research in Silver Spring, Maryland, the virus has evolved to a “minimal” degree since December.
“The coronavirus genome is exceptionally stable,” says Samuel DĂaz-Muñoz, an evolutionary virologist at the University of California, Davis. “Since the beginning of the pandemic we’ve seen like six mutations in a 30,000-base genome. It’s one strain with minor variations.”
This is probably down to two key factors: a relatively slow mutation rate and the fact that most mutations are a hindrance to the virus and so are weeded out.
As yet there is no conclusive evidence that any of the clades has progressed to become what virologists call a “strain” – that is, a biologically different entity, perhaps a more virulent one.
One mutation, D614G, attracted attention in May after an , perhaps because it was more transmissible though possibly less deadly. However, that remains an unproven claim. According to the Walter Reed team, all the currently circulating viruses are sufficiently similar that a successful vaccine will immunise against them all.
But as the virus spreads ever further, there are signs of different strains emerging. Three recently reported cases of reinfection in , and were caused by mutants that are all sufficiently different to evade the patients’ immune memory. These may constitute the first new strains of SARS-CoV-2, and go on to form distinct branches of its family tree. But only time will tell.
