A number of previous reports have suggested that the new coronavirus has mutated, but recent research has suggested that this may be misread.

On March 3, the National Science Review sponsored by the Chinese Academy of Sciences published a paper entitled "On the origin and continuing evolution of SARS-CoV-2".

In the dissertation, the largest genome-wide molecular evolution analysis of 103 new coronaviruses has found that 149 mutations have occurred in the virus strains, of which 101 can be classified into two subtypes, L and S.

The S type is a relatively older version, while the L subtype is more aggressive and more contagious. In terms of proportion, the L subtype is more common, reaching 70%, and the S subtype accounts for 30%.

Not a recent mutation

It is worth noting that, at noon today, according to leiphone.com, the industry media BioArt team analyzed the research of the relevant scientific research team and said that some of the media's "new coronaviruses have been mutated" are misread.

They said that the correct understanding should be: the new coronavirus can be divided into two types, L and S, according to different mutation sites in the genome, but these two types of mutations may have existed in the early stages of the virus outbreak, not recent mutations.

So what is going on? This has to go back to the paper itself.

S subtype is the "ancestor" of L subtype

A total of 103 viral genome sequences were selected for this study. It was found that the virus strain had 149 mutations, including 43 synonymous mutations and 83 nonsynonymous mutations, and 70% of the viruses the sequence has seven identical sense mutations, plus one identical missense mutation (L84S), which affects the function of the six proteins of the virus.

Spectrum analysis of derived mutations of 103 new coronavirus strains, orange is a non-synonymous mutation, and green is a synonymous mutation (Image from the paper)

The study classified these 70% of the viruses with these mutations as the L subtype of SARS-CoV-2 (L is derived from the missense mutation L84S); the S84L is called the S subtype.

The author of the paper believes that, based on the evolution of the new coronavirus, there may be a large difference in the transmission ability and severity of disease of the L and S subtypes.

To further study the relationship between L-type and S-type strains, the researchers reconstructed their phylogenetic trees based on the entire genome sequence of 103 SARS-CoV-2 viruses.

Evolutionary tree of 103 new coronavirus strains (Figure from the paper)

This further confirmed the differences between the two subtypes.

In the SARS-CoV family, the sequence of other earlier viruses is S84L. Therefore, the research suggests that the L subtype that is currently popular evolved from the S subtype, and the S subtype is actually the "ancestor" of the L subtype.

It is worth noting that the research analysis concluded that the two subtypes did not undergo cyclic reorganization in nature; SNP analysis further confirmed this lineage classification. 72 virus sequences were T28144, which encodes L; 29 virus sequences were C28144, which encodes S.

The L type is the T base (corresponding to leucine, Leu), and the S type is the C base (corresponding to serine, Ser).

By comparing with other coronaviruses, the authors found that the new S subtype coronavirus is closer to the bat-derived coronavirus on the evolutionary tree, and thus concluded that the S subtype is relatively older.

The L subtype was more common in the early stages of the Wuhan outbreak, and the frequency of the L subtype decreased after early January 2020. The authors believe that human intervention may exert greater selective pressure on the L subtype, and without these interventions, the L subtype may be more aggressive and spread faster.

On the other hand, because the selection pressure is relatively weak, the older and less aggressive S-types may have increased in relative frequency.

A natural reasoning is that the relatively old S-type coronavirus should produce more strains because it has more time to spread among the population.

However, genomic data indicate that L-type accounts for 70% and S-type accounts for 30%, and each L-type virus strain carries relatively more neonatal mutations than S-type.

Why do relatively young L-type coronaviruses produce more strains? The authors speculate that L-type viruses are more capable of transmitting or replicate faster in humans, which could mean they are also more virulent.

There are differences in the temporal and spatial distribution of the two new coronavirus subtypes (Image from the paper)

The authors further compared the changes in the proportion of S-type and L-type before and after January 7. They found that the proportion of L-type in the virus strain decreased while the proportion of S-type increased.

Regarding this somewhat abnormal change, the author also gave his own hypothesis-because China has adopted strong anti-epidemic measures, patients with type L virus may be more likely to show symptoms and thus more likely to be subject to manual intervention, thus making L The new type of coronavirus is under greater negative selection pressure, and the number of people infected is reduced.

In addition, these 103 samples showed that most patients were infected with only one of the L or S subtypes. However, a virus strain isolated from one of the American patients with a recent travel history in Wuhan suggests that they may be infected with both the L and S subtypes of new coronaviruses.

However, the authors say that the possibility of new mutants cannot be ruled out at this time.

Overall, this study systematically elucidated the evolutionary dynamics of the virus during human transmission through the genome analysis of 103 SARS-CoV-2.

At the same time, the authors point out that these findings mean that there is an urgent need for further comprehensive studies combining genomic data, epidemiological data, and chart records of clinical symptoms of patients with coronavirus in 2019.

Viral mutations in line with normal epidemiological rules

Nonetheless, the news has stirred everyone's hearts. Will the virus make the outbreak worse if the virus mutates? For a while, the discussion on the new type of coronavirus mutation on Zhihu and Weibo was aroused.

In this regard, BioArt gives a more convincing statement:

On the one hand, researchers need to bring more authoritative and professional explanations (It is necessary to mention that we all know that scientific research is more of a process of "proposing hypotheses-verifying hypotheses-negating hypotheses-then proposing new hypotheses", Therefore, we should also give more tolerance to scientific researchers, because the original research is constantly improved and developed);

On the other hand, in this age where everyone is a media, how to adhere to the bottom line, not blindly interpret scientific conclusions, and not disseminate irresponsible content is also something that every individual on the node of the communication chain must think about.

In addition, the author of the paper particularly emphasized that the new coronaviruses are not newly mutated to differentiate into L and S types, but these two mutant types may have existed in the early stages of the virus outbreak. It is the current isolation and medical measures that may be more harmful The L-shaped frequency is reduced. This result shows that the current strategies and measures for epidemic prevention and treatment are completely correct and effective.

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