New Research about Convergent Evolution of SARS-CoV-2 in Human and Animals

2021-05-11 Hits(531)

More than a year since the outbreak of the SARS-CoV-2, several highly publicized new variants have been generated with mutations in the viral genome. Among them, 501Y.V1 (B.1.1.7), 501Y.V2 (B.1.351), and 501Y.V3 (P.1) have dominated the re-rising number of cases in the UK, South Africa, and Brazil, respectively, triggering public concern about a new outbreak.

April 30, 2021 - Aiping Wu's team at the Suzhou Institute of Systems Medicine (ISM) and Chengfeng Qin's team at the Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, jointly published a review article Convergent evolution of SARS-CoV-2 in human and animals in the journal Protein & Cell, proposing the convergent evolution of SARS-CoV-2 variants in human and animal adaptation and exploring the possibility of using this phenomenon to prospectively capture potential adaptive loci for SARS-CoV-2 variants.


Research process


Different new variants contain different signature mutations within their genomes. However, the researchers noted that for the three relatively evolutionarily distant variants 501Y.V1, 501Y.V2 and 501Y.V3, N501Y is a signature mutation shared by all three variants. Coincidentally, the N501Y mutation also appeared during the adaptation of SARS-CoV-2 to mice. They found that using an early SARS-CoV-2 strain as the initial virus and passing it through successive generations in the lungs of aged mice resulted in the emergence of a set of adaptive mutations such as N501Y. Deep sequencing showed that the N501Y mutation appeared in the virus quasispecies after one pass in the lungs of mice, and the proportion of the N501Y mutation in the virus quasispecies gradually increased in subsequent passages, with the N501Y mutation dominating the quasispecies by the sixth generation.



Another coincidence is that the characteristic mutation K417N/T, shared by 501Y.V2 and 501Y.V3, also appeared in subsequent successive mouse passaging experiments and rapidly replaced the N501Y-only strain as the dominant variant. This observation in mice is also consistent with the sequential order of appearance of the N501Y and K417N/T mutations in the population. In the population epidemic, viruses containing only the N501Y mutation were first detected in Brazil on April 7, 2020, in the United States on April 21, and in the United Kingdom on June 8, 2020, while viruses containing both N501Y and K417N S protein mutations were first detected in October 2020.


Research Results


In summary, by analyzing the association of recent SARS-CoV-2 variants in animals and populations, the investigators concluded that SARS-CoV-2 have independently evolved to select for some of the same adaptive mutation loci during their adaptation to animals and populations, respectively. Since there are currently more than 20,000 mutated loci in the population, the vast majority of them may not be significantly associated with virus adaptation in the host. In the paper, the researchers also suggest that based on the convergent evolutionary patterns of SARS-CoV-2 in animals and populations, it may help to filter the random "noise" in such a large mutation pool, allowing us to select potentially critical loci that are closely associated with virus adaptation in the host, and thus contribute to the prospective identification of mutations and the development of control strategies.


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