GJ.1.2.6 saltation with ORF1a:A967V, ORF1a:T1168I, ORF1a:A3956S, ORF1b:S1552G, S:K97N, S:F456L and ORF8:A65V (20 seqs, USA, Canada, Netherlands)

[NkRMnZr]

Defining Mutations: GJ.1.2.6 > C3165T(ORF1a:A967V/nsp3_A149V), C3768T(ORF1a:T1168I/nsp3_T350I), C4777T, G12131T(ORF1a:A3956S/nsp8_A14S), A18121G(ORF1b:S1552G/nsp14_S28G), G21853T(S:K97N), T22928C(S:F456L), C26894T, C28087T(ORF8:A65V) Query: C3165T, C4777T, T22928C Earliest seq: 2023-10-06 (EPI_ISL_18415781, Arizona, USA) Latest seq: 2023-11-07 (EPI_ISL_18522371, Noord-Brabant, Netherlands) Sampled Countries: USA (7: AZ/2; CO/2; UT/2; NJ), Canada (BC), Netherlands (NB)

Genomes:

`EPI_ISL_18415781, EPI_ISL_18425012, EPI_ISL_18453124, EPI_ISL_18469939, EPI_ISL_18498259, EPI_ISL_18498265, EPI_ISL_18507763, EPI_ISL_18522371, EPI_ISL_18533131`

Mutation Profiles:

List of mutations on nearest phylogenetic branch

nuc unique  C3165T, C4777T, A18121G, G21853T
nuc homoplasies C3768T, T22928C, C26894T
ORF1ab  unique  A967V, S5953G
ORF1ab  homoplasies T1168I
S   unique  K97N
S   homoplasies F456L

List of mutations to root/reference strain

UShER: https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_38359_ec36c0.json?label=id%3Anode_4018162

Trivia:

• The Lazy XBB.2.3* finally got S:T478R and S:F456L
• The saltation should also contain G12131T(ORF1a:A3956S/nsp8_A14S) and C28087T(ORF8:A65V) due to potential dropout/low-coverage from USA/CO-CDPHE-41441538/2023|EPI_ISL_18507763|2023-10-15

[FedeGueli]

My easy bet this comes from Philippines. we will see!

[FedeGueli]

Alternative query to exclude spike dropouts : C3165T, C4777T, A18121G ( it gives the same result but please keep it here to double check low quality sequences

[jasondorjeshort]

What's with ORF8:A65V? This lineage has an intact ORF8, but this has evolved convergently also in multiple lineages (FU.2, JD.1.1) after the orf8 stop? It doesn't look like it's in an overlapping frame with another protein - how is this possible?

[ryhisner]

What's with ORF8:A65V? This lineage has an intact ORF8, but this has evolved convergently also in multiple lineages (FU.2, JD.1.1) after the orf8 stop? It doesn't look like it's in an overlapping frame with another protein - how is this possible?

I think that region of ORF8 is particularly prone to APOBEC-drive C->T mutations, particularly C28087T and C28093T. APOBEC3 disproportionately deaminates cytosines that are unpaired and on prominent stem-loops in the secondary RNA structure. It also occur much more commonly in certain nucleotide contexts. C28087T is unpaired, on a prominent stem-loop, and has a relatively good nucleotide context. I don't think ORF8:A65V or ORF8:S67F are adaptive at all; they're just located in positions in the genome that are prone to C->T mutations.

[FedeGueli]

+2 US

[FedeGueli]

13 now

[FedeGueli]

One sample only from December closing it for now.