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cov-lineages / pango-designation

Repository for suggesting new lineages that should be added to the current scheme
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BN.1.4 Sublineage with S:G261V, S:T678I, ORF3a:I37T, ORF3a:P240S, ORF8:D75G, & ORF1a:T4175I (80 seq) #1417

Closed ryhisner closed 1 year ago

ryhisner commented 1 year ago

Description

Sub-lineage of: BN.1.4 Earliest sequence: 2022-10-5, Scotland — EPI_ISL_15926883 Most recent sequence: 2022-11-23, Iceland — EPI_ISL_15983428, EPI_ISL_15971029 Countries circulating: Scotland (17), USA (4), Iceland (2), Germany (2), Australia (1), Ireland (1), Northern Ireland (1), Wales (1) Number of Sequences: 29 GISAID Query: Spike_K356T, Spike_T678I, Spike_G261V, NS3_I37T CovSpectrum Query: Nextcladepangolineage:BN.1.4* & S:G261V & S:T678I Substitutions on top of BN.1.4: Spike: G261V, T678I ORF3a: I37T, P240S ORF8: G75D ORF1a: V3367I, T4175I (NSP5_V104I, NSP9_T35I) ORF1b: T284I (NSP12_T275I) Nucleotide: A10132T, T11773C, C12789T, G10364A, C14318T, G22344T, C23595T, T24850C, T25502C, C26110T, A28117G

USHER Tree https://nextstrain.org/fetch/raw.githubusercontent.com/ryhisner/jsons/main/BN.1.4%20%2B%20G261V%2C%20T678I%2C%20ORF3aI37T%2C%20ORF3aP240S%2C%20ORF8D75G%2C%20etc%20-%20%20subtreeAuspice1_genome_39dd0_b0e70.json

image

Evidence This is a pretty impressive saltation, particularly for such a relatively young lineage. S:T678I seems to be on the rise in a number of lineages. ORF3a is a major region for T-cell epitopes, so these may be immune-evasion mutations. ORF1a:T35I is one of the most convergent ORF1ab mutations in chronic-infection sequences, and it’s remarkable that the other two ORF1ab mutations here—which are not a part of the saltation but are shared with >150 other BN.1.4 sequences—are NSP5 and NSP12 mutations, the MPro and RdRp proteins.

The most recently uploaded sequence, from Wales, has S:T323I, ORF1a:H134R, and ORF1b:R1600L.

Genomes

Genomes EPI_ISL_15713956, EPI_ISL_15713980, EPI_ISL_15758932, EPI_ISL_15811931, EPI_ISL_15837145, EPI_ISL_15854260, EPI_ISL_15878329, EPI_ISL_15878334, EPI_ISL_15878362, EPI_ISL_15905040, EPI_ISL_15909588, EPI_ISL_15909626, EPI_ISL_15909802, EPI_ISL_15909848, EPI_ISL_15918103, EPI_ISL_15926883, EPI_ISL_15926884, EPI_ISL_15926886, EPI_ISL_15960802, EPI_ISL_15971029, EPI_ISL_15971653, EPI_ISL_15974545, EPI_ISL_15983428, EPI_ISL_15989564, EPI_ISL_16011020, EPI_ISL_16011052, EPI_ISL_16011298, EPI_ISL_16024934, EPI_ISL_16028687
Mydtlwn commented 1 year ago

What is the role of the mutation at site 75?

ryhisner commented 1 year ago

@Mydtlwn, my guess is that the ORF8:G75D mutation plays no role at all. Stop codons that pretty much eliminate ORF8 have been really common—in Alpha, for example—and they don't seem to cause any disadvantage at all. It seems like SARS-CoV-2 could chuck ORF8 entirely without it causing any harm.

Mydtlwn commented 1 year ago

thx

thomasppeacock commented 1 year ago

Recommending this for assignment as i) its still clearly growing ii) its pretty widespread and iii) fairly clear evidence of a (mini) saltation

FedeGueli commented 1 year ago

74 seqs as today. i would like to highlight that S:678I was in a quite fast BA.5.1 sublineage that was not designated cause arose too late to compete with S:346Ters but it seemed fast enough to compete withOrf1b:1050N.