XDF/XCM recombinant(3 seq, Germany, Puerto Rico, Canary Island)

[aviczhl2]

@AngieHinrichs, there seems to be a new EG.5.1/XCM recomb with XCM Spike. Please add it into usher list.

EPI_ISL_18373945 Germany

EPI_ISL_18406963 Puerto Rico

XCM+T331G(rev),C335T,C1387T,T3453C,T4234C(rev), T5730C(rev), G5720A, A6536G(rev), C9693T, A11782G, C12789T,C13560T(rev)

Orf1a:H22Q(rev),R24C,V1063A,G1819S,I1822T(rev),S2091G(rev),A3143V,T4175I

The Pureto Rico seq has Orf1a:1-288 masked.

XDF --XCM Breakpoint between 13561 and 16877

T331G(rev),C335T,T3453C,T4234C(rev), T5730C(rev), G5720A, A6536G(rev), C9693T, A11782G, C12789T,C13560T(rev) from a branch in XDF

C1387T is private.

GISAID query: C1387T,T3453C,A29558G No. of seqs: 2(Germany, Puerto Rico)

EPI_ISL_18373945 Germany, 2023-9-14

EPI_ISL_18406963 Puerto Rico,2023-9-25

updated usher

[corneliusroemer]

A bit more analysis would be useful - I have no clue where the breakpoints of this would be, what the donors are etc

[aviczhl2]

A bit more analysis would be useful - I have no clue where the breakpoints of this would be, what the donors are etc

Yeah will analyse them when a 2nd one appears. For the 1st one just posting here for @AngieHinrichs to keep it on the tree if it shows >5 "reversions".

[FedeGueli]

A bit more analysis would be useful - I have no clue where the breakpoints of this would be, what the donors are etc

yes this is just to track them and be sure not being invisible. be safe i will ping on everything that grows.

[corneliusroemer]

@aviczhl2 when I check whether a potential recombinant I spot has already been reported, it's very useful if the country/ies where the first samples were found is included in the issue title as well. Also, it's much easier to read strain names than epi isls, so if you could include the strain names as well, that would be super useful. Thanks!

[aviczhl2]

Reopen as there seems to be 2nd seq. Puerto_Rico/PR-CVL-020145/2023/EPI_ISL_18406963 from Puerto Rico, analysing.

[aviczhl2]

It seems that 1st part is not purely EG.5.1 but also formed via some form of recomb. There's too many candidates for the 1st part,

So we have ?--EG.5.1--(XBB.2.3--DV.7.1=XCM) for this variant, fantastic.

[FedeGueli]

Thank you i ve put it under monitoring.

[Over-There-Is]

~Germany/BE-RKI-I-1137446/2023|EPI_ISL_18241633|2023-08-28 EG.10.1+C335T, del510_518 could be a good candidate (England/CLIMB-CM7YF34S/2023|EPI_ISL_18072102|2023-07-19)~

[Over-There-Is]

~France/HDF-IPP15717/2023|EPI_ISL_17831422|2023-06-05 FW.2+C335T, del510_518 USA/OK-OKPHL-0027623/2023|EPI_ISL_18073387|2023-05-03 XBB.1.5+del510_518, C1387T Canada/BC-BCCDC-640618/2023|EPI_ISL_18129124|2023-07-23 XBB.1.5+C335T, del510_518(USA/ID-USAFSAM-S20973/2023|EPI_ISL_16550312|2023-01-05, USA/WI-MCRI-013085/2023|EPI_ISL_17195575|2023-02-10, USA/MI-SHMSU-A05_I_0144_71/2023|EPI_ISL_18335297|2023-04-06)~

[aviczhl2]

France/HDF-IPP15717/2023|EPI_ISL_17831422|2023-06-05 FW.2+C335T, del510_518 USA/OK-OKPHL-0027623/2023|EPI_ISL_18073387|2023-05-03 XBB.1.5+del510_518, C1387T Canada/BC-BCCDC-640618/2023|EPI_ISL_18129124|2023-07-23 XBB.1.5+C335T, del510_518(USA/ID-USAFSAM-S20973/2023|EPI_ISL_16550312|2023-01-05, USA/WI-MCRI-013085/2023|EPI_ISL_17195575|2023-02-10, USA/MI-SHMSU-A05_I_0144_71/2023|EPI_ISL_18335297|2023-04-06)

Yeah many candidates for 2/3, but none has 3/3 so unable to confirm.

[FedeGueli]

no new sequence closing it for now

[aviczhl2]

+7 from Spain and Germany

[aviczhl2]

The new seqs belong to a new recomb of this one and FL.20.1, this one is still 2 though.

[aviczhl2]

del509_517 doesn't appear in #1050, so it shall not be included in this lineage.

[aviczhl2]

Now the first part is limited to C335T and C1387T, however still cannot confirm. One branch of XBB.1.5 has both mutations but also having T1753C, so shall not be the donor. This lineage shall get one from its XBB donor while privately acquired another.

[FedeGueli]

great team work @aviczhl2 @nkrmnzr @Over-There-Is

[FedeGueli]

Closing this for now.

[aviczhl2]

+1 Canary Island

[corneliusroemer]

If someone could write down a proper analysis of breakpoints of this one and evidence for having multiple donors, that would be great. In particular, we'd want to know how many private mutations and reversions are saved by assuming a new donor/breakpoint. Are we sure it's XCM that's a parent here? XCM is very rare, and very rare until recently. Would be quite unlikely to be a donor, especially in such a complex way. Are we missing something simpler?

[aviczhl2]

Private mutations should be: C335T,510-518del,,C1063T,C1387T,G2407A,T3453C,C8318A,A11782G,C21648T, yes it is from XCM having : T17661C,A18879G,A24373G,A29558G in common with it BPI 1-11783 : unknown 11784- 17760 : EG.5.1 17661 - end XCM

T3543C and A11782G comes from a particular EG.5.1 branch. The breakpoint 1 is between 2335 and 3542.

5' recomb of EG.5.1 and something else is very very common. There's even an XCR branch of this. https://github.com/sars-cov-2-variants/lineage-proposals/issues/1077

There is also a large undesignated 5'--EG.5.1 recomb branch with 50+ samples https://github.com/sars-cov-2-variants/lineage-proposals/issues/1088

Small unproposed branches are numerous.

[aviczhl2]

If someone could write down a proper analysis of breakpoints of this one and evidence for having multiple donors, that would be great. In particular, we'd want to know how many private mutations and reversions are saved by assuming a new donor/breakpoint. Are we sure it's XCM that's a parent here? XCM is very rare, and very rare until recently. Would be quite unlikely to be a donor, especially in such a complex way. Are we missing something simpler?

If we assume this is EG.5.1/XCM recomb then we have to put both C335T,C1387T(one of them can be explained by the 5' XBB donor) and T2334C(rev) to private mutations as they don't show up in the T3543C,A11782G branch of EG.5.1 .

So we may save 2 mutations(including one reversion) by assuming a third donor at 5'.

[aviczhl2]

But, yeah it depends on how to view the chance of orf1a:690 reversion and potential 5' recomb events of EG.5.1.

[aviczhl2]

If someone could write down a proper analysis of breakpoints of this one and evidence for having multiple donors, that would be great. In particular, we'd want to know how many private mutations and reversions are saved by assuming a new donor/breakpoint. Are we sure it's XCM that's a parent here? XCM is very rare, and very rare until recently. Would be quite unlikely to be a donor, especially in such a complex way. Are we missing something simpler?

For XCM donor I'm quite sure though.

This one is exactly the same as XCM from 13561. It contains the XBB.2.3 part and the DV.7.1 part with the XCM-specific breakpoint, so cannot be something else.

[aviczhl2]

@FedeGueli It turns out only the Germany seq has del510_518, C1063T and C21648T. The new Canary Island seq confirms that by unmasking and not having del510_518 and C1063T. These shall not belong to the whole recomb.

[aviczhl2]

@FedeGueli It turns out only the Germany seq has del510_518, C1063T and C21648T. The new Canary Island seq confirms that by unmasking and not having del510_518 and C1063T. These shall not belong to the whole recomb.

Yeah thank you. there is something weird in the covspectrum comparison i m trying to understnad what is driving it not reliably.

It shows everything with more than 50% prevalence. So everything appearing in 1/2 of the seqs will be shown.

Also it has not included the new Canary Island seq, which clears up a lot of mess as the Puerto Rico seq has the 5' part masked.

[FedeGueli]

Now it is quite clearer: https://cov-spectrum.org/explore/World/AllSamples/Past3M/variants?es%2FPast3M%2Fvariants%3FnextcladePangoLineage=HK.3*&nucMutations=C1387T%2CT3453C%2CA29558G&nextcladePangoLineage1=XCM*&nucMutations2=A11782G%2CT3453C&nextcladePangoLineage2=EG.5.1*&analysisMode=CompareEquals&

Recomb pvt: C1387T common with EG.5.1 + T3453C : C335T,T3453C,G5720A,C9693T,A11782G,C12789T common with XCM: T17661C,A18879G,C22033A,A22115G,A22190G,T22200G,G22331A,A22893C,T22917G,G22927T,T22928C,C24134A,A24373G,T24991A,G25606A,C25721T,T25959C,A29558G

[aviczhl2]

Current usher. It seems clear that C1063T, A2407G and T21648C are Germany-seq only.

usher

[FedeGueli]

Please correct me if i messed up it again. but it seems likely: the EG.5.1 donor was in germany already in mid september when XCM started to spread

[FedeGueli]

I deleted the wrong messages check only the last ones please

[aviczhl2]

Please correct me if i messed up it again. but it seems likely: the EG.5.1 donor was in germany already in mid september when XCM started to spread

I think this recomb likely formed at somewhere without sequencing with a low-level circulation. So it only outputs a little outside,

[FedeGueli]

But, yeah it depends on how to view the chance of orf1a:690 reversion and potential 5' recomb events of EG.5.1.

They have been inherited by the EG.5.1. donor i am checking the tree.

https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_170bc_cf7f70.json?c=gt-ORF1ab_690&gmax=21555&gmin=266&label=id:node_3535124

yeah confirmed: the branch you found with T3453C has S:A690V reverted to A! @aviczhl2 check everything but if this is the case it is very clear recombinant between this EG.5.1 and XCM with one breakpoint only

[aviczhl2]

But, yeah it depends on how to view the chance of orf1a:690 reversion and potential 5' recomb events of EG.5.1.

They have been inherited by the EG.5.1. donor i am checking the tree.

Oh I realized.

It may also be the largest branch in #1088 with additional C1387T !!!

1088 is EG.5.1+C335T,T2334C(rev), and the largest branch has T3453C as well.

[FedeGueli]

But, yeah it depends on how to view the chance of orf1a:690 reversion and potential 5' recomb events of EG.5.1.

They have been inherited by the EG.5.1. donor i am checking the tree.

Oh I realized.

It is the largest branch in #1088 with additional C1387T !!!

wait wait this should be recombinant of two recombinants!??!???!?!?!??!?! (thank you great work and sorry for the initial mess!)

[aviczhl2]

This looks more clear.

The upper branch is XCV, lower is #1088 which is the donor of this recomb. It is also a recomb branch and it shares the T2334C(rev) with XCV while having additional C335T.

[aviczhl2]

@corneliusroemer I think after some discussion and analysing the newly-uploaded Canary Island seq this recomb is clearer.

It is a recomb of #1088 (a newly-emerged XBB/EG.5.1.3 recomb) and XCM.

Final recomb tower.

[FedeGueli]

@corneliusroemer I think after some discussion and analysing the newly-uploaded Canary Island seq this recomb is clearer.

It is a recomb of #1088 (a newly-emerged XBB/EG.5.1.3 recomb) and XCM.

Final recomb tower.

Great work ! I am amazed by this side of the tree went on recombining multiple times in so short times none of the lineage being widespread! Wondering if some Cruise ship involved or some sub-population . very weird.

[aviczhl2]

Great work ! I am amazed by this side of the tree went on recombining multiple times in so short times none of the lineage being widespread! Wondering if some Cruise ship involved or some sub-population . very weird.

Actually it is a 2-step recomb like XCT. #1088 and XCM meets to form #944, while #944 and FL.20.1 meets to form #1050.

I think the formation of #944 is quite normal, both #1088 and XCM are not small branches. And it is clear that #1088 first gets some mutations before recombining to form #944, so the formation of #1088 shall be totally unrelated with #944. Just a normal recomb event with both donors from a sizeable branch. Special is that both donor branches are recomb of recombs, but that can happen.

The 2nd step may be involved on cruise ship or somewhere that enhances recombination like navy or jail or universities, as that specific small branch of FL.20.1 forms multiple recombinants almost at the same time.

[corneliusroemer]

This one's still just 3 sequences, right? Bit small for designation, so holding off for now.

[aviczhl2]

This one is likely died off. Its children is growing though..