BM.1.1.4 (S:K356T, S:T572I) Sublineage with S:L452R, ORF1b:V2406I (12 seq, Feb 21)

[ryhisner]

Description

Sub-lineage of: BM.1.1.4
Earliest sequence: 2022-12-12, Bhutan — EPI_ISL_16984438
Most recent sequence: 2023-2-12, Singapore — EPI_ISL_16975343
Countries circulating: Bhutan (10), Singapore (2—but both with travel history from Malaysia)
Number of Sequences: 12
GISAID Query: G20683A, C14805T, G29527A, C912A, A2151C, -C3037T
CovSpectrum Query: Nextcladepangolineage:BM.1.1.4* & !C3037T & [5-of: C1102T, C14805T, G20683A, C7945T, A9343G, T22917G, C29200T]
Substitutions on top of BM.1.1.4:
Spike: L452R
ORF1a: V2406I
Nucleotide: C1102T, C14805T, G20683A, C7945T, A9343G, T22917G, C29200T
Nucleotide Reversion (likely Usher tree artifact): T3037C

USHER Tree
https://nextstrain.org/fetch/raw.githubusercontent.com/ryhisner/jsons/main/BM.1.1.4%2BL452R_subtreeAuspice1_genome_127cb_49add0.json

Evidence
This lineage appears to be dominant in Bhutan and is likely widely circulating in Malaysia and perhaps elsewhere in SE Asia. Eleven of the 12 sequences in this lineage have been uploaded in the past two days (February 20-21). Ten were uploaded today from Bhutan. One additional sequence from Bhutan uploaded today has ORF1b:V2406I but not S:L452R. Of the 11 sequences uploaded today from Bhutan collected January 1, 2023 or later, 10 are from this lineage. The most recently collected sequences here are from Singapore (collection dates Feb 5 and Feb 12), and both have travel history with Malaysia.

Six of the 10 sequences from Bhutan are listed as having had travel history in prior months. However, the earliest sequence, from December 12, had no travel history in prior months. I'm guessing the high percentage of subjects with travel history is due to such people being more likely to be sequenced. All indications are that this is in wide circulation locally.

The large number of additional mutations in this branch likely indicate this has been spreading undetected for some time. Many of the mutations are quite interesting, including S:T22N (2 seq), S:T76I (1), S:G181A (1), S:Y266C (1), S:A348T (1), S:S704L (2), ORF3a:L53F (1), ORF3a:T64I (1), ORF1a:P4120S/NSP8P178S (9), N:P6L (1), N:G34R (1), and N:P151S (1).

I think there is likely a mistake in the BM.1.1.4 Usher tree. As pictured below, this branch and one other nearby branch of BM.1.1.4—which is probably worthy of designation in its own right—lack the nucleotide mutation C3037T. Since reversion is unlikely, I'm guessing these two branches belong together, though perhaps I'm overlooking something.

Genomes

Genomes

EPI_ISL_16899330, EPI_ISL_16975343, EPI_ISL_16984438, EPI_ISL_16984442, EPI_ISL_16984443, EPI_ISL_16984445, EPI_ISL_16984446, EPI_ISL_16984447, EPI_ISL_16984448, EPI_ISL_16984449, EPI_ISL_16984450, EPI_ISL_16984451

[corneliusroemer]

You're too fast @ryhisner ;) - I was just about to open an issue and see you've already got one out!

I get a different coloring of 3037 - in my case the top branch (with European sequences) has T, and isn't reverted either. So the reversion seems to be a Bhutan artefact (as the Singapore sequence doesn't have that reversion either):

Strange, maybe many of the sequences have N and so Usher imputes? Maybe @AngieHinrichs can enlighten us what's going on!

In your tree, the Singaporean sequences also have the reversion... In mine they don't:

[corneliusroemer]

3037T dates back to the very early pandemic - it's in B.1, almost always present:

Ah, I think I got it - Usher seems to be masking this site. So results depend on how you upload data. Whether you get samples that are on the tree already or place new ones.

[c19850727]

14 seqs now. 2 newly uploaded from Singapore, both with recent travel history from Malaysia.

[AnonymousUserUse]

Milestone EP.1 missing

[FedeGueli]

18 sequences as today 2 new ones from Bhutan and two more from Singapore travel related with Thailand and Malaysia.
Being this likely spreading in an undersampled area and carrying a combo of mutations in key residues better flagging it. @thomasppeacock