sars-cov-2-variants / lineage-proposals

Repository to propose and discuss lineages
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JN.1 + ORF1a:S1534C (A4864G, A4865T) [11 seq, 5 countries, 2 continents] #1363

Closed ryhisner closed 5 months ago

ryhisner commented 7 months ago

Description

Sub-lineage of: JN.1.1 (BA.2.86.1.1.1) Earliest sequence: 2023-12-23, India, Maharashtra — EPI_ISL_18718954 Most recent sequence: 2024-1-12, USA, New York — EPI_ISL_18847618 Continents circulating: Asia (8), North America (3) Countries circulating: India (5), USA (3), Malaysia (1—traveler to Singapore), Nepal (1), Singapore (1) Number of Sequences: 11 GISAID Nucleotide Query: A4864G, A4865T, C897A CovSpectrum Query: Nextcladepangolineage:JN.1* & [2-of: A4864G, A4865T] Substitutions on top of JN.1.1: ORF1a: S1534C (NSP3_S716C) Nucleotide: A4864G, A4865T

USHER Tree https://nextstrain.org/fetch/raw.githubusercontent.com/ryhisner/jsons2/main/JN.1.1__A4864G_A4865T.json?c=gt-ORF1ab_1534&gmax=21555&gmin=266&label=id:node_6876893

Most of the branches here are just artifactual reversions, so there's in reality very little diversity here.

image

Evidence I don't expect this to be a significant lineage, but I want to at least register it here because there's something strange about these two nucleotide mutations. Both are rare: The synonymous A4864G has been in just 666 sequences while A4865T has been in just 88 sequences, yet 35 sequences have had both A4864G and A4865T.

image

Furthermore, 17 of those 35 sequences also have G4868A, and these represent at least 7 independent lineages with these three mutations. G4868A is also rare, appearing in only 1169 sequences.

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It's hard to make sense of. Is it possible that the repeat GTGT causes an RdRp stutter and makes it lay down a third GT? And could the same be happening with G4868A, only with two repeat TATA motifs causing the change? It seems very unlikely, but I can't think of any other explanation.

Perhaps there is a strong secondary RNA structure here that any one of these mutations greatly disturbs but which the two (or three) mutations together do not alter? Or else they replace the old secondary structure with a new one that also serves the same purpose? I really don't know.

Genomes

Genomes EPI_ISL_18605120, EPI_ISL_18718954, EPI_ISL_18725649-18725651, EPI_ISL_18726196, EPI_ISL_18819819, EPI_ISL_18847333, EPI_ISL_18847618, EPI_ISL_18848542, EPI_ISL_18856232
aviczhl2 commented 5 months ago

Likely dead. However two Chinese seq under JN.1.1 also have this mutation too, seems a bit convergent.