A Kozak-related non-coding deletion effectively increases B.1.1.7 transmissibility

Abstract

AbstractThe high transmissibility acquisition of SARS-CoV-2 Variant of Concern (VOC) B.1.1.7 remains unclear and only mutations in coding regions have been examined. We analyzed 875,338 high-quality SARS-CoV-2 genomic sequences and the epidemiology metadata. The occurrence of a non-coding deletion (g.a28271-) in the B.1.1.7 background immediately causes the rapid spread of B.1.1.7. The number of B.1.1.7-like strains lacking the deletion is significantly less than that of B.1.1.7 strains (n = 259 vs 92,688, P-value< 4.9 × 10−324). The same highly significant statistics is observed in different countries, gender and age groups. However, the deletion alone does not cause such high viral transmissibility. The deletion and another mutation (g.gat28280cta) co-affect translational efficiency of the genes N and ORF9b by changing the core Kozak sites. The deletion interacts synergistically with S:p.P681H and S:p.T716I to increase viral transmissibility. Therefore, the Kozak-related non-coding deletion, also carried by the Delta VOC, is crucial for the high viral transmissibility of SARS-CoV-2.