Sinickle
commented
2 years ago The main reason this genome stands out to me is the S:417T + S:444N combo, but having two additional spike mutations and having spread to 4 continents while likely being from an under-sequenced area makes this more worthwhile to designate than other larger S:417T + S:444N combo lineages, in my opinion.
Bloom labs believes S:444 is one of the most important sites to watch for mutations for, as a method of achieving immune escape. I claim that S:444N becomes more beneficial after S:417T is acquired.
The following tool does not show all sequences, but is hopefully sufficient for the argument.
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It contains 6100 Omicron+S:417T and 115 Omicron+S:444N. There are 58 sequences that have both.
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Omicron sequences with S:417T appear to have subsequently independently acquired S:444N at least 6 times
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3 of these 6 times, the child sublineage was sequenced at least 5 times
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S:444N appeared independently on any Omicron 51 times
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Of these 51 times, only 3 times did it have at least 5 child sequences. These are the same 3 times that it also had S:417T.
Since Omicron with S:417T has never made up even 4% of cases for a time period, I believe these numbers argue that S:444N is more likely to succeed when S:417T is present.
This possibility makes it important to monitor a lineage that has this pair of mutations.
shay671
chrisruis
FedeGueli
silcn
agamedilab
bitbyte2015
This lineage is now up to 122 sequences and is placed next to a new interesting sublineage with K444N and F157S that has 63 sequences. 157 has been seen to confer a growth advantage on its own. Seeing that the number of sequences continues to grow and this branch has now spawned a second interesting spike profile, I think that this should be designated
corneliusroemer
c19850727
InfrPopGen
Credit to @bitbyte2015 for being the original one (to my knowledge) to find these sequences!
This potential sublineage features interesting mutations that make it distinct, and although it has been sequenced just 7 times, it has been found in Brazil, Australia, USA, and Japan (but the Japanese sequences were in travelers from India)
Description
Potential sublineage of: BA.2.38 (the Indian sublineage with spike 417T from a BA.2 root)
Gene | Amino changes -- | -- ORF1b | D51N Spike | K147E, K444N, I692LEarliest sequence: 2022/05/06 (Australia)
Most recent sequence: 2022/05/22 (USA-California)
Mutations on top of BA.2:
nextstrain tree [cov-Spectrum query]
The lineage I'm proposing is the one in the red box. Since the parental lineage, BA.2.38 without 6091T, is most predominant in India, and the Japanese cases in my proposed lineage are confirmed to be from India-related travel, it seems likely that this lineage is more prominent in India despite never being sampled there. Additionally, this lineage is 5 nucleotide mutations away from any possible parental sequence which likely implies lack of sampling of intermediaries rather than a true evolutionary jump. The Indian sequences not in the red box in the screenshot share just 1 synonymous nucleotide mutation, and several unique ones -- I believe that the right thing to do here would be to include the Indian non-red box sequences as regular BA.2.38 in the classifier training set, and the red box ones as the new proposed lineage, which would be defined by T7153C + the previously listed AA mutations.
Proposed sublineage: EPI_ISL_13175338, EPI_ISL_12808436, EPI_ISL_12808434, EPI_ISL_13027402, EPI_ISL_12808520, EPI_ISL_13027403, EPI_ISL_12767836
Regular BA.2.38 that share T7153C (think including these in the training set might improve specificity of the proposed lineage, especially since one of these also obtained S:444N independently.): EPI_ISL_12953126, EPI_ISL_12953226, EPI_ISL_12953163, EPI_ISL_12953161
EDIT: As others point out in the comments below, another notable branch has formed, starting at the S:444N mutation. If my proposed branch is designated, we should be careful that the other branch doesn't get misclassified.