BA.5.2 (ORF1b:T1050N) Sublineage with S:G446D, S:N460K, & ORF1a:A1679V (32 seq, 22 with S:K147Q)

[ryhisner]

Description

Sub-lineage of: BA.5.2 (ORF1b:T1050N)
Earliest sequence: 2022-9-15, Mongolia — EPI_ISL_15299167
Most recent sequence: 2022-11-1, Mongolia — EPI_ISL_15688016
Countries circulating: South Korea, Mongolia, England, Singapore, Japan
Number of Sequences: 17
GISAID Query: Spike_G446D, Spike_N460K, NSP13_T127N
CovSpectrum Query: Nextcladepangolineage:BA.5.2* & ORF1b:T1050N & S:G446D & S:N460K
Substitutions on top of BA.5.2 (T1050N):
Spike: G446D, N460K
ORF1a: A1679V (NSP3_A861V)
Nucleotide: C5301T, C15933T, G22899A, T22942G

USHER Tree
https://nextstrain.org/fetch/raw.githubusercontent.com/ryhisner/jsons/main/BA.5.2%20%2B%20G446D%20%2B%20N460K%20%2B%20ORF1aA1679V%20-%20subtreeAuspice1_genome_15915_c25cd0.json

Evidence
This lineage, like the one I proposed in Issue #1311, seems to extend back to the root of the BA.5.2 (T1050N) branch. Both lineages share S:G446D, but they diverge from there. In fact, as you can see on the downsampled global Usher tree below, Usher wants to put this lineage (along with Issue #1131) in an entirely separate branch from the other BA.5.2 + ORF1b:T1050N branch, which seems absurd. This looks like a real conundrum to me, and I don’t know what the true phylogenetic tree of this lineage should look like.

Bizarrely, the regular Usher tree places this lineage 73 mutations away from the original SARS-CoV-2, but the downsampled global tree puts it 98 mutations away. I don't know how to explain this.

Five sequences in this lineage have come from Mongolia—including the two most recent sequences—which indicates this lineage could be much more widespread than its 17 sequences would lead us to believe.

And of course S:N460K seems to be the key that allows any lineage that acquires it to accumulate additional spike mutations. Over half of this lineage already has S:K147Q, and I wouldn’t be surprised to see many more NTD and RBD mutations soon.

Genomes

Genomes

EPI_ISL_15299167, EPI_ISL_15312995, EPI_ISL_15351813, EPI_ISL_15492011, EPI_ISL_15492830, EPI_ISL_15493554, EPI_ISL_15493634, EPI_ISL_15533895, EPI_ISL_15533946, EPI_ISL_15533997, EPI_ISL_15534505, EPI_ISL_15607930, EPI_ISL_15607933, EPI_ISL_15672651, EPI_ISL_15676879, EPI_ISL_15683037, EPI_ISL_15688016

[ryhisner]

First sequence in North America from this lineage came into today. It's on the S:K147Q branch and came from California, USA. EPI_ISL_15766758

EDIT: Later yesterday, a second sequence, again from the S:K147Q branch, was uploaded from Washington state, USA.

[ryhisner]

Six sequences from this lineage uploaded from South Korea today, all with S:K147Q. This brings the total number of sequences to 32, of which 22 have S:K147Q.

[FedeGueli]

I re-discovered the wheel this morning with this sublineage : after acquiring S:147Q it seems going faster and spreading in South Korea i noticed one sequence from Japan and that led me here!:

43 sequences on Usher as today:
https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_1d656_1c72f0.json

@thomasppeacock @AngieHinrichs @corneliusroemer @InfrPopGen i think this should be designated soon is a different way for the virus to reach the same fitness using 147 (BA.2.75 teaches) and 446 (as BA.1 or Bh.1) and homoplasic S:460K (from 22942G as Ba.2.75)

51 seqs found on Gisaid

it shows some advantage vs other s:460k carrying lineages in South Korea : https://cov-spectrum.org/explore/South%20Korea/AllSamples/Past3M/variants?aaMutations=S%3AN460K&aaMutations1=ORF1a%3AA1679V%2CS%3AN460K%2CS%3AG446D%2COrf1b%3A1050N&analysisMode=CompareToBaseline&

[InfrPopGen]

Thanks for submitting. We've added lineage BA.5.2.43 with 31 newly designated sequences, and 0 updated designations. Defining mutation C5301T (ORF1a:A1679V) (following T22942G (S:N460K) on current tree).