FedeGueli
commented
8 months ago a possible growth advantage Comparison to JN.1.5: https://cov-spectrum.org/explore/World/AllSamples/Past3M/variants?nextcladePangoLineage=JN.1.5*&nucMutations1=G17278A%2CT17279C%2CC5986T%2CC6026T&analysisMode=CompareToBaseline&
alurqu
Over-There-Is
Transferring Pre-Proposal 1228 on request from @FedeGueli.
Proposing a JN.1.5 sublineage with C5986T, and ORF1a:P1921S (NSP3:P1103S; C6026T) first detected in Ticino, Switzerland.
As of 2024-01-30, Cov-Spectrum reported 142 good-quality (221 total) JN.1.5+ORF1a:1921S+5986T sequences. Source: https://cov-spectrum.org/explore/World/AllSamples/AllTimes/variants?nextcladeQcOverallScoreTo=29&variantQuery=nextcladePangoLineage%3AJN.1.5*+%26+ORF1a%3AP1921S+%26+C5986T&
This lineage has been reported from 4 continents and shows a possible growth advantage over its parent JN.1.5. While this lineage has been detected in stellar sequencing countries Canada and Singapore, the majority of the global sequences are not from these two countries so their relatively intense sequencing is not likely to be biasing the global growth advantage. The plurality of sequences for this lineage are from Malaysia where this lineage's growth relative to its parent JN.1.5 is unimpressive but possibly due to this sublineage already dominating JN.1.5 in that country.
However, in Singapore which has submitted the second-most sequences of this sublineage (66 on CoV-Spectrum as of 2024-01-30), this sublineage shows a growth rate relative its parent JN.1.5 of 42% (confidence interval 22 to 69%).
Checking Bloom and Neher's data https://jbloomlab.github.io/SARS2-mut-fitness/ and https://github.com/jbloomlab/SARS2-mut-fitness/blob/main/results/aa_fitness/aamut_fitness_by_clade.csv, as shown below ORF1a:P1921S is associated with a relative growth advantage for all clades. As a novel 2-nucleotide mutation, ORF1b:V1271T has no data in the Bloom and Neher dataset.
As of 2023-12-25, UShER showed all of the CoV-Spectrum samples are on a single subtree with evidence of additional branching:
To visualize on UShER: https://nextstrain.org/fetch/github.com/alurqu/pango-designation-support-alurqu/raw/main/2023/12/subtreeAuspice1_genome_CoV-Spectrum_JN.1%2BORF1a_1921S%2BORF1b_1271T%2B5986T.json?c=gt-ORF1ab_1921&label=id%3Anode_6802619
GISAID query: G17278A, T17279C, C5986T, C6026T
First GISAID sequence: Ticino, Switzerland 2023-11-17
Most Recent GISAID sequence: Singapore 2024-01-22
A zip archive of CoV-Spectrum-derived UShER output files for these sequences as of 2023-12-25 is available at Support-JN.1+ORF1a_P1921S+ORF1b_1271T+5986T.zip
A CoV-Spectrum list of GISAID EPI ISLs for good-quality sequences as of 2023-12-25 is available at gisaid-epi-isl-JN.1+ORF1a_P1921S+ORF1b_1271T+5986T.txt
Potential effects of the non-synonymous mutation ORF1a:P1921S on viral relative fitness
From the clade-specific Bloom and Neher estimates (from https://github.com/jbloomlab/SARS2-mut-fitness/blob/main/results/aa_fitness/aamut_fitness_by_clade.csv) of the fitness effects of the non-synonymous mutations, for ORF1a:P1921S:
clade,gene,aa_mutation,delta_fitness 20A,ORF1ab,P1921S,0.45975 20B,ORF1ab,P1921S,1.1701 20C,ORF1ab,P1921S,1.0042 20E,ORF1ab,P1921S,0.9422 20G,ORF1ab,P1921S,0.42036 20I,ORF1ab,P1921S,0.78364 21C,ORF1ab,P1921S,0.46398 21I,ORF1ab,P1921S,0.57457 21J,ORF1ab,P1921S,0.85523 21K,ORF1ab,P1921S,0.82125 21L,ORF1ab,P1921S,0.75162 22A,ORF1ab,P1921S,0.89186 22B,ORF1ab,P1921S,0.83121 22C,ORF1ab,P1921S,0.53524 22D,ORF1ab,P1921S,0.58985 22E,ORF1ab,P1921S,0.84586 22F,ORF1ab,P1921S,1.1764 23A,ORF1ab,P1921S,0.75612 23B,ORF1ab,P1921S,0.057158 23D,ORF1ab,P1921S,0.78267
ORF1a:P1921S has a positive fitness effect for all clades with the strongest positive fitness effect in clades 22F, 20B, 20C, and 20E and a weak likely negligible effect in clade 23B.
As of this writing, Bloom and Neher provide no relative fitness estimates for ORF1b:V1271T. However, for some clades ORF1b:V1271L and ORF1b:V1271A are associated with positive relative fitness impacts with some of the impacts, such as ORF1b:V1271L, having significant positive relative fitness impacts such as +1.6328 in clade 22B and +1.448 in clade 22C. So mutations at ORF1b:V1271 are plausibly beneficial to viral fitness.