The Qian Wenfeng team of the Chinese Academy of Sciences reveals: the new crown Omicron strain has undergone evolution in domestic mice

Source | JGG Editor | Wang Duoyu Typesetting | Shui Chengwen On November 24, 2021, a new mutant strain of the new coronavirus, Omicron, was reported in South Africa and other places
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In just two days, the strain was judged by the World Health Organization as a "variant of concern" (VOC)
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As of December 16, 2021, 89 countries and regions around the world have found confirmed cases of Omi Kiron strain, and the infection rate of this strain is significantly faster than the Delta strain
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Unlike other variants that require high attention (Alpha, Beta, Gamma, and Delta), Omi Keron strains appear to carry a large number of rare mutations that are rarely reported
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Researchers did not find its "close relatives" in the database of the new coronavirus variant strain, so the source of the Omi Keron strain has attracted widespread attention in the scientific community
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There are currently three mainstream hypotheses regarding the source of the Omi Keron strain: The first hypothesis is that the Omi Keron strain has been “secretly” spread for a long time in an area where nucleic acid testing and sequencing has not been adequately carried out, leading to its discovery.
Many mutations have been accumulated at that time
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The second hypothesis is that the Omi Kiron strain may have undergone long-term evolution in a certain immunodeficiency patient (such as a patient who has received long-term chemotherapy or AIDS), and therefore has a large number of rare mutations
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The third hypothesis is that the "ancestors" of the Omi Keron strain may have "overflowed" from humans to other animals, and passed back to humans after a period of evolution in the organism, so it carries a large number of rare mutations in the population
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 On December 24, 2021, the research team of Qian Wenfeng from the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences published a research paper titled “Evidence for a mouse origin of the SARS-CoV-2 Omicron variant” in the Journal of Genetics and Genomics online
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The study revealed that the transmission route of the Omi Keron strain is most likely to be transmitted from humans to domestic mice and back to humans after long-term evolution
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The research first carried out an evolutionary analysis of the Omi Keron strain's genome and identified 45 mutations in the ancestral sequence of the Omi Keron strain
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On this basis, using the mutation spectrum (that is, the relative proportions of 12 different base mutation types) to trace the virus host, it was found that the mutation spectrum of the Omi Keron strain and the new coronavirus evolved in the human body (including immunodeficiency patients) There are significant differences in the resulting mutation spectrum
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Surprisingly, the mutation spectrum of Omi Kiron strain is highly similar to that of murine hepatitis viruses, indicating that Omi Kiron strain may have evolved for a long time in domestic mice
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If the Omi Kiron strain did evolve for a long time in domestic mice, then the Omi Kiron strain will have mutations in its genome that can adapt to transmission in domestic mice
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Based on this idea, the study detected the mutation of the Omi Keron strain on the spike protein that can determine the range of host infection, through the new coronavirus sequence isolated from 18 mammals (such as mink and white-tailed deer).
By comparison, it was found that these mutations had the highest degree of overlap with the mutations of the new coronavirus isolated from house mice
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The study further molecularly docked the receptor binding domain of the spike protein with 32 kinds of mammalian receptor proteins, and found that the mutation carried by the Omi Keron strain was the most significant in enhancing the affinity of the mouse receptor protein
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Analysis of the virus genome and protein affinity of Kiron Omi strain, A: The mutation spectrum of Kiron Omi strain is similar to that of murine coronavirus, which is significantly different from the evolution of coronavirus in the population (ellipse shows 95% confidence interval) ); B: Mutations on the spike protein of Kiron strain (purple marker) are enriched at the interface between the receptor binding domain (RBD) of the spike protein and the cell receptor (ACE2); C: with the patient Compared with the new coronavirus isolated in, the affinity of the Omi Keron strain RBD with the ACE2 protein of house mice has increased significantly
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Based on the above results, it is speculated that the ancestor of the Omi Keron strain was passed from humans to domestic mice roughly in mid-2020, after more than a year of evolution in domestic mice, and returned to humans at the end of 2021
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The discovery of this transmission route provides inspiration for future new crown epidemic prevention and control strategies
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Graduate students of the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences Wei Changshuo, Shan Kejia and Wang Weiguang are the co-first authors of the paper, Zhang Shuya is the co-author, and associate researcher Yun Qing and researcher Qian Wenfeng are the co-corresponding authors
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Related work was funded by the National Natural Science Foundation of China
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Link to the paper: https://doi.
org/10.
1‍016/j.
jgg.
2021.
12.
003, open for reprinting, welcome to forward to Moments and WeChat groups