Science and Technology

On the origin of this species

TV Jayan | Updated on May 09, 2021

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A search is on for ‘patient zero’ — the first ever case of Covid-19 — as a team of genetic sleuths attempts to trace the mutation history of the deadly SARS-CoV2 virus

The novel coronavirus, which has caused untold miseries in almost every country in the world over the last one and a half years, is still shrouded in many mysteries. Even after nearly 15.7 crore cases and around 32.7 lakh deaths, scientists are still in the dark about the emergence of the very first case of human transmission.

Identifying the very first case — what scientists call ‘patient zero’ — is key to ascertaining how the virus SARS-CoV2 acquired the ability to infect humans. Besides, it can help draw up the evolutionary history of the virus, which has brought the world economy on its knees in a short span of time.

Now a team of genetic sleuths, led by an India-born scientist in the US, may have unearthed some clues that could help build the pedigree chart of SARS-CoV2. To do this, Sudhir Kumar, an alumnus of the Birla Institute of Technology and Science, Pilani, used molecular genetic tools that can help calculate the age of mutations. He used computational methods that were developed to determine the mutational history of tumour cells in a patient.

Kumar is the Founding Director of the Institute for Genomics and Evolutionary Medicine and professor at the departments of biology and computer and information sciences at Temple University in Pennsylvania, USA. He has played a key role in developing techniques for analysing mutations in cancer patients. In a paper published in the Molecular Biology and Evolution, Kumar and seven other experts note that multiple coronavirus infections in China and the US harboured the progenitor genetic fingerprint in January 2020 and later, “suggesting that the progenitor was spreading worldwide months before and after the first reported cases of Covid-19 in China”.

This coronavirus changes every two weeks, on average. “This is why we hear about new variants all the time, and it is why currently circulating variants are different from the first coronavirus strain that infected the patient-zero. By identifying the progenitor of all the strains that have infected humans since 2019, we can know the genetic composition of the virus in patient-zero,” says Kumar.

The mother virus

By comparing the progenitor genome — the mother of all SARS-CoV2 coronaviruses — with the strains involved in major outbreaks, Kumar says scientists can find out whether it was directly involved in the earliest human outbreaks or if one of its variants (offspring) was the reason. Their finding was that the Covid-19 infections in Wuhan in December 2019 were caused by a strain that evolved by three mutations of the progenitor. “Wuhan was the first detected major outbreak (or super-spreader event) caused by an offspring of the progenitor in 2019. We found that the progenitor was also present around that time in the coronavirus family of strains, just as grandparents, parents, and children are around simultaneously in families.”

Kumar, who did his PhD under Masatoshi Nei, the noted Japanese-American evolutionary biologist known for his genetic distance theory between various populations, says the progenitor strain has clinical significance as it tells us about the minimum genetic changes from its relative viruses (found in bats and other species) that occurred to make it so dangerous to humans.

“Using the progenitor genetic fingerprint, we can build a progression of changes in its offspring strains that have quickly infected millions worldwide. Using a map of changes, we can identify mutations that make the virus more transmissible or escape treatment and vaccines,” Kumar tells Quantum.

The mutational order analysis tool that they used is very unique. It has a simple and intuitive way of categorising mutations — strains and sub-strains. For example, alpha mutations were the first to happen in the progenitor and they produced the strain that was first found in Wuhan in December 2019. The coronaviruses carrying the alpha mutations then got beta mutations to create the ancestors of the strains that are now infecting the world, including the most recent Indian strain (B.1.617). So, the coronaviruses currently infecting Indians have alpha-plus-beta ancestry, Kumar said.

Mutational history

In the study, the scientists estimated that the progenitor SARS-CoV2 was circulating worldwide at least 6-8 weeks before the Wuhan outbreak, indicating that by October 2019, the progenitor had already spread around the world. “This estimate can go back further if coronavirus is found in hospital samples being investigated from 2019. If their genomes contain any of the mutations found in the Wuhan coronaviruses, then the timeline of the progenitor will shift to the summer of 2019. We need a retrospective sampling of coronaviruses to make the timeline firmer,” says Kumar.

Explaining the mutational order analysis tool further, Kumar says a freshly mutated particle carries the new mutation as well as all the mutations that its parent carried. This is the reason why all the coronavirus variants containing beta mutations also contain all the alpha mutations. “This happens because the coronavirus evolution is clonal, as the offspring comes directly from one parent (The virus does not require two parents, as we humans do.) This means that the mutation that occurred the earliest (in 2019) would be found in all the coronavirus infections, and later mutations will be found in fewer infections. This is indeed true, as alpha mutations have the highest frequency, followed by beta and other mutations,” he explains.

The reconstructed mutational history of SARS-CoV-2 has shown how the virus has mutated spatially and temporally. Projecting this into the future, one can broadly predict what kind of mutations to expect.

The authors of the paper say that this approach can be gainfully employed not just for the coronavirus, but all pathogens.

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Published on May 09, 2021

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