Desi expert traces ‘great grandpa’ of SARS-CoV-2

Where there is no sample, there is data. The effort to trace the origins of SARS-CoV-2, which causes Covid-19, would not have been as exacting had ‘patient zero’ been found by now. In January this year, the World Health Organisation said we might “never find who patient zero was.” But there was a way to identify the ancestor of the virus, a molecular epidemiologist from India found — by “predicting” history with data. And the ancestor, or progenitor genome, it turned out, had been around since at least October 2019 and survived till March 2020.

The progenitor is the genome of the coronavirus found in that one person who spread it to other people, and then everyone else got descendants of that coronavirus. “Once large amounts of data from SARS-CoV-2 patient infections began to be accumulated, everyone was curious about

new strains

that were observed after December 24, 2019 (when the first case was reported). We wanted to know which strain came first, the progenitor,” Dr Sudhir Kumar, director of the Institute for Genomics and Evolutionary Medicine,

Temple University

, told TOI. “We can tell you the time of the ancestor’s origin was around or before October 2019.” Two months before the first case, predating by a wide margin the reference genome sequence that is being used now, called Wuhan-1.

But the progenitor did not die out immediately. “We found it was still going around after the offspring, SARS-CoV-2, started spreading. It was present in China (Fujian, Guangdong, and Hangzhou) in January 2020 and the US (New York) in March 2020,” said Kumar, who is originally from Delhi. So, the ancestor virus did not need a mutation to infect, spread and survive. “It was ready to go on its own … SARS-CoV-2 is its great-grandchild, three mutations away.”

To arrive at this, Kumar and his team adapted a process called mutation order analysis, which is often used to study mutations in tumours. The findings have been published in the Oxford Academic journal ‘Molecular Biology and Evolution.’

They went over 1,74,000 genomes over a year in three batches. “We lined up the genomes and stack them on top of one another, genome by genome. Then, we looked across a particular position across genomes, say position 1, and saw what was happening,” Kumar said. “By stacking genomes of infections of 100,000 people, we looked for positions with differences (or mutations). If there was a difference, we saw how frequently that occurred — in 20% of the samples? 10%? 5%? Once we had this information, our software could infer the mutation tree all the way back to the first mutation … So, you take the data and predict history — how many steps the virus took and what the changes were.”

With this approach, they found seven major lineages of the progenitor and assigned letters of the Greek alphabet to identify each — Nu, Alpha, Beta, Gamma, Delta and Epsilon. These lineages help explain the trajectories of the variants so far and the likely paths they could take. “Alpha 1 was the first major mutation of the coronavirus. Then came Nu 1, but Nu 1’s progeny disappeared — some viruses grow, others do not. Then came the Beta mutation. There are three Beta variants. The Beta cluster entails that very famous spike protein, Beta 2. Many think that it made it more transmissible,” Kumar explained. “The B.1.617 strain, prevalent in India, is a child of the Beta cluster.” And while Asian strains seem to have driven the pandemic, going by the analysis, variants that evolved from them are now infecting Asia much more.

But Kumar urged caution while associating a strain with greater transmissibility. “You could observe many people with a particular variant and say that it is more infectious. But, it is not possible to say for sure whether it is because of the mutation itself. Say, for instance, someone with a B.1.618 variant attends a large gathering, and the number of cases explodes. That may have nothing to do with the transmissibility variant alone,” he said. And, what the mutation tree they mapped establishes is the extent to which allowing the virus to spread strengthens its numbers. He added, “By now, we know that SARS-CoV-2 undergoes 24 changes a year. So, someone infected with the coronavirus will have a new strain in the body within two weeks. If we allow the virus to replicate by getting infected, it will mutate in our bodies. We will be spreading the mutant form. At some point, there might be a mutant that is not affected by vaccines — though that does not appear to be a problem right now. But by not spreading the virus, by not letting it evolve, you eventually kill it."