SARS-CoV-2 as a product of genetic recombination and purifying selection

One of the important pieces of knowledge about coronavirus is its origins, closest relatives, and the differences between them and SARS-CoV-2.

It is known that SARS-CoV-2 shares the highest level of genetic similarity (96.3%) with CoV-RaTG1, a virus sampled from the bat in Yunnan, 2013. SARS-CoV-2 appears to share fewer similarities with pangolin viruses such as Pan_SL-CoV_GD and Pan_SL-CoV_GX (91,2% and 85,4% genetic similarity). The team of scientists from USA analyzed 43 coronavirus genetic sequences, including SARS-CoV, Bat_SL-CoV, SARS-CoV-2, and
Pan_SL-CoV from three different clades.

It was discovered, that despite the high genetic similarity of SARS-CoV-2 and RaTG13, their S-protein sequences are quite different. However, RBM aminoacid sequences in S1 SARS-CoV-2 subunit and Pan_SL-CoV_GD are almost identical. Researchers also noted that while SARS-CoV and SARS-CoV-2 sequences are quite different, their S1 sequences are very similar.

SARS-CoV and SARS-CoV-2 infiltrate the cells with the help of S-protein, while RaTG is unable to use that mechanism. Viruses capable of infecting human cells have a similar S1 amino acid structure.

Scientists conclude that SARS-CoV-2 is likely to originate from RaTG13, then it acquired the cell infiltration mechanism with S-protein by recombination with a virus similar to Pan_SL-CoV_GD.

Researches also discovered the similarities in amino acid sequences of SARS-CoV-2, RaTG13 and all Pan_SL-CoV in the regions before and after RBM until a certain S2 aminoacid. This discovery implies the effect of purifying selection. Similar signs of purifying selection have also been found in other genome regions.

Viruses can be grouped by genes that were affected by the selection: SARS-CoV-2, RaTG13, all Pan_SL-CoV, and two bat coronaviruses show similar selection patterns in genes M and E. ORF1a and ORF1b selection mechanisms are the same for SARS-CoV-2, RaTG13 and some Pan_SL-CoV. This indicates the evolution mechanisms are similar for coronaviruses of different animals.

Thus, human MERS-CoV, SARS-CoV and SARS-CoV-2 originated by recombination, researchers conclude. Purifying selection and recombination are used for quick adaption to new hosts. The source of SARS-CoV-2 remains unknown, but now allowing the direct contacts with wild animals will prevent the appearance of new zoonosis infections.

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