| A Noncoding A-to-U Kozak Site Change Related to the High Transmissibility of Alpha, Delta, and Omicron VOCs |
| 論文作者 |
Yang, JN; Cui, YM; Yu, DL; Zhang, GQ; Cao, RF; Gu, ZL; Dai, GY; Wu, XX; Ling, YC; Yi, CY; Sun, XY; Sun, B; Lin, X; Zhang, Y; Zhao, GP; Li, YX; Pan, YH; Li, HP |
| 期刊/會議名稱 |
MOLECULAR BIOLOGY AND EVOLUTION |
| 論文年度 |
2023 |
| 論文類別 |
Article |
| 摘要 |
Three prevalent SARS-CoV-2 variants of concern (VOCs) emerged and caused epidemic waves. It is essential to uncover advantageous mutations that cause the high transmissibility of VOCs. However, viral mutations are tightly linked, so traditional population genetic methods, including machine learning-based methods, cannot reliably detect mutations conferring a fitness advantage. In this study, we developed an approach based on the sequential occurrence order of mutations and the accelerated furcation rate in the pandemic-scale phylogenomic tree. We analyzed 3,777,753 high-quality SARS-CoV-2 genomic sequences and the epidemiology metadata using the Coronavirus GenBrowser. We found that two noncoding mutations at the same position (g.a28271-/u) may be crucial to the high transmissibility of Alpha, Delta, and Omicron VOCs although the noncoding mutations alone cannot increase viral transmissibility. Both mutations cause an A-to-U change at the core position -3 of the Kozak sequence of the N gene and significantly reduce the protein expression ratio of ORF9b to N. Using a convergent evolutionary analysis, we found that g.a28271-/u, S:p.P681H/R, and N:p.R203K/M occur independently on three VOC lineages, suggesting that coordinated changes of S, N, and ORF9b proteins are crucial to high viral transmissibility. Our results provide new insights into high viral transmissibility co-modulated by advantageous noncoding and nonsynonymous changes. |
| 期 |
6 |
| 卷 |
40 |
| 影響因子 |
10.7 |
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