outbreak.info
outbreak.info copied to clipboard
Please display aa mutations on alternative-frame ORFs (encoding accessory proteins)
Many SARS-CoV-2 proteins are not encoded in the canonical frame used by outbreak.info to track amino acid mutations, but instead on highly-conserved alternative open reading frames including ORF9b (overlapping N) and ORFS.iORF1/2 (overlapping S): https://www.sciencedirect.com/science/article/pii/S0042682221000532
These non-canonical ORF proteins are as highly (or more) expressed than many canonical ORF proteins: https://www.sciencedirect.com/science/article/pii/S0092867421007017
Mutations on canonical ORFs are common, indicating possible non-synonymous mutations on non-canonical, alternative-frame ORFs: for example, lineage-defining mutations in Beta (S:D80A), Alpha and BA.4/5 (S:delHV69); and in Delta (N:D63G), Omicron (N:P13L, N:del31/33). It is possible that the non-synonymous mutations on the alternative-frame ORFs are more important for fitness than the corresponding mutations on the canonical ORFs.
Further, synonymous mutations on the canonical ORFs (which are not tracked by outbreak.info) may be non-synonymous in the alternative frames. That means outbreak.info does not currently track all relevant mutations, and cannot be used to do so until it covers the non-canonical open reading frames including ORF9b and ORFS.iORF1/2.