JD.1 Sublineage with S:A475V, ORF8:A65V, ORF1b:A241V (32seq, Aug 25)—originally found by @oobb45729

[ryhisner]

Description All credit goes to @oobb45729 for being the first to discover this branch and for proposing its parent branch. The only reason I created (then closed) this issue was because I was fooled by the incorrect Usher tree placement into thinking this was a different lineage.

Sub-lineage of: JD.1
Earliest sequence: 2023-7-8, USA, Florida — EPI_ISL_18012368
Most recent sequence: 2023-8-21, Spain, Basque Country — EPI_ISL_18134783
Countries circulating:
Number of Sequences: ~32
GISAID Nucleotide Query: C14189T, A14634G, C19185T, T28282C
CovSpectrum Query: Nextcladepangolineage:JD.1* & [4-of: C14189T, A14634G, C19185T, G22927T, T22928C, C22986T, T28282C]
Substitutions on top of JD.1:
Spike: A475V
ORF8: A65V
ORF1b: A241V (NSP12_A250V)
Nucleotide: C14189T, C19185T, C22986T, C28087T

Phylogenetic Order of Mutations: C14189T (ORF1b:A241V) → C28087T (ORF8:A65V) → C19185T, G22927T, T22928C, C22986T, T28282C (S:L455F, S:F456L, S:A475V, ORF1b:A241V)

USHER Tree
https://nextstrain.org/fetch/raw.githubusercontent.com/ryhisner/jsons/main/JD.1_A475V.json?c=gt-nuc_22986&label=id:node_7177834

Evidence
The benefits of the FLip (S:L455F, S:F456L) in XBB lineages is famous already, but S:A475V has been far less common. It is an escape mutation, and according to @Asinickle, is located extremely close to 455-456. A475V has also shown up recently in other scattered L455F-F456L lineages, so perhaps the Flip opens the door to A475V, which previously, judging by its rarity, must have imposed a steep fitness cost.

One really interesting detail: this lineage—like its parent, JD.1—has T28282C, which is synonymous in N but substantially upgrades the ORF9b Kozak sequence—from worst to best at the -2 spot—so this should somewhat increase the expression of ORF9b, a theme that has occurred again and again throughout the pandemic.

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Genomes

Genomes

EPI_ISL_17979082, EPI_ISL_18033321-18033322, EPI_ISL_18037173, EPI_ISL_18070073, EPI_ISL_18072815, EPI_ISL_18072818, EPI_ISL_18072823-18072824, EPI_ISL_18092160, EPI_ISL_18094726, EPI_ISL_18095944, EPI_ISL_18098754, EPI_ISL_18105023, EPI_ISL_18105120, EPI_ISL_18106546, EPI_ISL_18110057, EPI_ISL_18113215, EPI_ISL_18118823, EPI_ISL_18119237, EPI_ISL_18119241, EPI_ISL_18119349, EPI_ISL_18119784, EPI_ISL_18121880, EPI_ISL_18123909, EPI_ISL_18124225, EPI_ISL_18124982, EPI_ISL_18130473, EPI_ISL_18134783, EPI_ISL_18134811, EPI_ISL_18134853, EPI_ISL_18134859

[ryhisner]

This looks like a duplicate that confused me because Usher made it look entirely separate from a bunch of other sequences that are probably related to it. My mistake.

[FedeGueli]

@ryhisner i was checking this but then fell.asleep while ushering. I see 17 seqs with the Trio 455-4566-475V they should be GK.3.1 plus the other undesignated xbb.1.5 flip

[FedeGueli]

@ryhisner if @oobb45729 agrees you can reopen this one as sublineage of the recently designated JD.1 cause it was a bit a messy designation cause Cornelius saw it from the Brazilian scientists which have correctly highlighted it , but we were tracking it thanks to OObb since it was 2 sequences only in another issue where we widely have spoken about this S:A475V sublineage . SO all the discussion is now buried and i fear this sublineage could not be tracked properly cause anyone finds it as already proposed but instead no one is aware of all the tale about this one. so Please reopen it after OOBB approval.

[oobb45729]

I am OK with it.

[FedeGueli]

I am OK with it.

Thank you! @ryhisner please reopen it as sublineage of JD.1

[FedeGueli]

By the way JD.1+475 jumped to 25 with my query (A14634G , T28282C ,C22986T) and 28 with your one Ryan (C14189T, A14634G, C19185T, T28282C)!
I think this should be urgently designated .

cc @corneliusroemer could you take a look at it? last doubling in our chart 10 days so in the very high range.

[ryhisner]

I've tried to edit the title and description and Usher trees to correct all the previous mistakes, but I'm in a rush and am certain I've missed some and/or made other mistakes, but I'm reopening this issue at the urging of @FedeGueli & with the blessing of @oobb45729, to whom all credit for discovering and describing this lineage should go.

[FedeGueli]

Thank you @ryhisner ! That issue was long discussed and it is a good example how to monitor collectively something from just 2 sequences. It is hard and without much consideration outside but small clusters/linegeas tracking iis likely the main field of our work of variant spotters/Trackers.

[FedeGueli]

Designated JD.1.1 please @corneliusroemer add milestone-

[oobb45729]

The A475V branch was not found by me. Give credit to @FedeGueli.