Siteeraan GITHUB keskustelusta , josa tämä variantti mainitaan. Sitä on nyt 800 sekvenssiä.
(Ryhisner, last month)
XBB.1 Sublineage with S:E180V, S:K478R, S:S486P, ORF9b:I5T, ORF9b:N55S, ORF1a:L3829F, ORF1b:D1746Y (42 seq) #1723
Earliest sequence: 2023-1-23, USA, New York — EPI_ISL_16835403
Most recent sequence: 2023-2-24, India, Maharashtra—
EPI_ISL_17073064; Singapore (with travel from India) — EPI_ISL_17030043;
Denmark — EPI_ISL_17048705
Countries circulating: Primarily in India. Has been
sequenced in India (23), USA (7—at least five with international travel
history), Singapore (6—all with travel from India), England (2), Denmark
(1), Germany (1), Ireland (1), Italy (1),
Number of Sequences: 42
GISAID Query: T12730A, T28297C, A28447G
CovSpectrum Query: T12730A, T28297C, A28447G
Substitutions on top of XBB.1:
Spike: E180V, K478R, S486P
ORF9b: I5T, N55S
ORF1a: L3829F (NSP6_L260F)
ORF1b: D1746Y (NSP14_D222Y)
Nucleotide: C11750T, C11956T, T12730A, A14856G, G18703T, A22101T, A22995G, T23018C, T28297C, A28447G, C29386T
USHER Tree https://user-images.githubusercontent.com/33738461/222865638-e0a62e01-46df-48b4-8fe0-70cfe583e844.png
The Usher tree looks as if it has two very separate branches, but this
is an artifact from the very low spike coverage in most of the Indian
sequences here. The branches in the lower section of the tree consist
almost entirely of artifact reversions. Similarly, all the sequences
that appear to lack S:E180V merely lack coverage there and therefore
almost certainly possess it.
Evidence
This saltation lineage has already spread quite widely across the globe,
but of the non-Indian sequences with adequate metadata about travel
history, almost all indicate international travel, mostly from India.
One USA sequence lists travel history from Ethiopia, two with India, and
the rest do not specify a country (but are sequenced by Gingko
Bioworks, which only sequences incoming international travelers). All
six sequences from Singapore have travel history in India. Sequencing in
India has been rather sparse of late, so this may comprise a
substantial fraction of infections there, particularly given it was
first sequenced on January 23.
S:K478R has been present in a few smaller lineages
(CM.4.1, BA.2.38.3) and regularly appears in scattered sequences here
and there. ORF1a:L3829F is of course found in all BQ* sequences, but it
is also one of the most convergent ORF1a mutations found in
chronic-infection mutations. ORF9b:I5T (T28297C) is in XBB.1.9 and has
been posited to be the reason XBB.1.9 lineages seem to grow somewhat
faster than XBB.1.5. ORF9b has been implicated in immune evasion,
primarily interferon suppression I think, so it's possible ORF9b:N55S
could confer some further resistance to immunity. Both of these ORF9b
mutations are synonymous in N.
Genomes
FG to ryhisner: i m seeing a lot of S:478R mainly from SA Russia and in XBB.1.5 .
It was defining in BH.1 that with BJ.1 and Ba.2.10.4 was a main actor
the first era of heavy mutated BA.2 from Indian area won then by BA.2.75
and its recombinant XBB.' FedeGueli
commented
Mar 4, 2023
This saltation lineage has already spread quite widely across the globe, but of the non-Indian sequences with adequate metadata about travel history, almost all indicate international travel, mostly from India. One USA sequence lists travel history from Ethiopia, two with India, and the rest do not specify a country (but are sequenced by Gingko Bioworks, which only sequences incoming international travelers). All six sequences from Singapore have travel history in India. Sequencing in India has been rather sparse of late, so this may comprise a substantial fraction of infections there, particularly given it was first sequenced on January 23.
Genomes
It was defining in BH.1 that with BJ.1 and Ba.2.10.4 was a main actor the first era of heavy mutated BA.2 from Indian area won then by BA.2.75 and its recombinant XBB.'
@corneliusroemer @thomaspeacock @InfrPopGen @AngieHinrichs i suggest a very fast designation of this one to monitor it as soon as possible ( i already added it to internal charts and its growth is in the top range comparable to both XBB.1.9.1 and XBB.1.9.2 at the same number of seqs) , from its profile i bet it will compete with the other leading XBB.1+486P spikes
FG commented
Mar 4, 2023
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We didnt care too much to XBB.1.9 early advantage but that was then shown real, so i highlight you that the signal is present here too and clearly also against XBB.1.9 growth advantage: https://user-images.githubusercontent.com/87669813/222918520-d2b1168f-998a-4d4d-b461-c6bc3a36e886.png Ryhiarner: |
.., ORF9b overlaps with N (nucleocapsid) in the SARS-CoV-2 genome, but they are out of frame with respect to each other, meaning that a nucleotide mutation that results in an amino acid (AA) substitution in ORF9b does not always cause an AA substitution in N. Nucleotide mutations that cause an AA substitution are called non-synonymous. Those that do not cause an AA change are called synonymous. Everything below is a layman's simplification, some of which may not be precisely correct but which I think gets the basic picture right.
For example, the nucleotide mutation T28297 is the third nucleotide in N:N8, which has the nucleotide sequence AAT. T28297C changes the sequence for this AA to AAC. However, both AAT and AAC code for the same amino acid: asparagine (symbolized by N). So T28297C is synonymous in N. In ORF9b, T28297 is the 2nd nucleotide the 5th amino acid, ORF9b:I5, whose nucleotides are ATC. T28297C changes this from ATC to ACC, which results in a change in amino acid from isoleucine (I) to threonine (T).
https://user-images.githubusercontent.com/33738461/222920834-3556fe98-2293-4af5-83b6-0a16c352081b.png
You can see how N and ORF9b overlap in the diagram below, which I pasted together using screenshots from NextClade. The N gene spans nucleotides 28274-29533 while ORF9b stretches from 28284-28577. The RNA-dependent RNA polymerase (RDRP), which basically makes copies of each viral gene by creating a complementary RNA strand, runs along the genome, beginning at the 3' end (the far right side in the diagram below). Each of the genes pictured (except ORF1b) has its own code (called a transcription regulatory sequence, or TRS) near its 5' end (left side in diagram) that the RDRP can recognize as a signal to stop, latch onto the RNA, and begin scanning the other direction. When it reaches a start codon (the nucleotide sequence ATG), it starts creating the complementary RNA strand. When it reaches a stop codon (TAA, TAG, or TGA), it stops copying.'
Question:
Thanks a lot for the detailed explanation!
What is the range of ORF1a and ORF10? I have often heard of that, but
cannot find an answer for the exact range of these two genes.
Angie Hinrichs commented March 3
Q: What is the range of ORF1a and ORF10? I have often heard of that, but cannot find an answer for the exact range of these two genes.
Answer: The NCBI RefSeq https://www.ncbi.nlm.nih.gov/nuccore/NC_045512.2 includes gene annotations at the nucleotide coding level and the protein level (ORF1a and ORF1ab are each split into several small proteins), so if you search for ORF1a and ORF10 on that page you can find their ranges in the reference genome and some other info about them.
The RefSeq annotations for NC_045512.2 include only N (a.k.a. ORF9 or nucleocapsid), they don't divide it into ORF9a and ORF9b.
Nextstrain's annotations include ORF9b: https://github.com/nextstrain/ncov/blob/master/defaults/annotation.gff Beware, those annotations also artificially split ORF1ab into separate ORF1a (which is real) and ORF1b (which is not real) in order to avoid having to account for ribosomal slippage in ORF1ab when translating nucleotide changes to protein changes.
FedeGueli
commented
Mar 4, 2023
orf1a 1-4401
orf10 29558-end of genome (3' end)
here what u need: https://codon2nucleotide.theo.io/
Q:
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Summary:
CoV-Spectrum also uses the annotation from Nextstrain. Is so correct? ------edit 2023/3/5------ |
FedeGueli
commented
Mar 5, 2023
@InfrPopGen @corneliusroemer @thomasppeacock @AngieHinrichs
To better contestualize reccomended lineages @alurqu and me tried to add them to collection 24 to preview how they will rank min the global competion
https://cov-spectrum.org/collections/24
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