Quick reminder:
Tomorrow (Jan 3rd) is the abstract submission deadline for the 30th Viral dynamics and Evolution meeting.
dynamicsevolution.org/event/1/page/2
This year's meeting will be in Heidelberg in April!
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Richard Neher
@richardneher
i am a biologist/physicist at the in Basel trying to understand how microbes evolve. views are my own, RT!=endorsement.
@richardneher@mstdn.science
Richard Neher’s Tweets
Our paper regarding Omicron convergent evolution is out on .
In this story, we analyzed the immune evasion capability of ~50 convergent variants and explained how RBD mutations suddenly emerged convergently due to a more focused immune pressure.
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too bad this study wasn't posted on a preprint server -- the community would have had an opportunity to discuss the data and give feedback to the authors before it ends up in final form in a journal. 5/5
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The authors report a lot of interesting data and most of these data are consistent with the canonical picture of Omicron's spread. But the putative intermediates don't support the surprising claim of gradual evolution. 4/n
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Two of these sequences for example have mutation A23604G (P681R in Spike) that is characteristic of Delta -- a variant that dominated in August 2021. There are more such examples. 3/n
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The putative intermediates from Benin (BEN-1 to BEN-5) are low coverage and contain signature mutations of Delta and Omicron. Contamination is thus a more likely explanation of these unexpected sequences. 2/n
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This recent paper by Fischer et al
science.org/doi/10.1126/sc
claims that Omicron evolved in a step wise manner with circulating intermediates.
I am not convinced.
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This was a fun project with 🐘jbloom_lab@mstdn.science ! See Jesse's thread for a summary!
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In new study, we examine evolution of #SARSCoV2 mutation spectrum. biorxiv.org/content/10.110
TLDR: There have been changes in relative rates of mutations during SARSCoV2’s evolution, & mutation spectrum is becoming more similar to other sarbecoviruses.
Thread below.
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In new study, we examine evolution of #SARSCoV2 mutation spectrum. biorxiv.org/content/10.110
TLDR: There have been changes in relative rates of mutations during SARSCoV2’s evolution, & mutation spectrum is becoming more similar to other sarbecoviruses.
Thread below.
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Thank you very much for inviting me to this fantastic workshop with exciting science in beautiful St. Lucia!
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The 1st 
Workshop on SARS-CoV-2 Variants & Evolution #SACovidWorkshop22 kicks off today. 84 leaders in SARS-CoV-2 immunology, virology, epidemiology, evolution & vaccines from over 30 universities & institutes are gathering to share the latest advances in #Covid19 research.
Workshop on SARS-CoV-2 Variants & Evolution #SACovidWorkshop22 kicks off today. 84 leaders in SARS-CoV-2 immunology, virology, epidemiology, evolution & vaccines from over 30 universities & institutes are gathering to share the latest advances in #Covid19 research.
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I've written an essay with my views on how to balance risks & benefits in virology research: nytimes.com/2022/10/30/opi
Important to work together to arrive at regulations that maximize benefits of valuable research w/o creating new risks from potential pandemic viruses in lab.
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#INSaFLU update! In order to keep facilitating routine genome-based analyses of influenza, SARS-CoV-2, and other pathogens, we have just updated INSaFLU (insaflu.insa.pt) with important new features: integration of #Nextstrain and #algn2pheno !
👇
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A short update on how waning immunity and immune evasion by convergent mutants BQ.1.1 and XBB stack together. Data suggest that most serum obtained ~7.5 months after BA.1 breakthrough infection would hardly neutralize BQ.1.1 and XBB. (NT50 of 20 is the lower limit of our assay)
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While this paper is an interesting mechanistic study of mouse ACE2 binding, I respectfully disagree that it provides significant evidence supporting mouse origin of Omicron.
Below I explain my reasoning.
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We've been thinking that the Omicron variant evolved from an immunocompromised individual with accelerated in vivo mutations. A new report @PNASNews raises the potential that it emanated from mice -> humans
pnas.org/doi/full/10.10
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In work led by , we develop pseudovirus system to deep mutational scan full #SARSCoV2 spike: biorxiv.org/content/10.110
TLDR: can now safely measure how all mutations to viral entry proteins affect antibody neutralization.
🧵 below (1/n)
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Updating results regarding convergent variants BU.1, BR.2, BM.1.1.1, CA.1, and XBB.
XBB is currently the most antibody-evasive strain tested, and BR.2, BM.1.1.1, CA.1 are more immune evasive than BA.2.75.2 and BQ.1.1.
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1/3 #GenomeEditing #CRISPR
Lies and libel by : "These interests are generally not disclosed in discussions on the EU’s GMO regulations."
greens-efa.eu/en/article/doc
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This study on response to Omicron after #SARSCoV2 vaccination provides some optimism re “original antigenic sin” biorxiv.org/content/10.110
TLDR: although response to Omicron dominated by preexisting B-cells, antibodies from these cells better at 6 months than 1 month.
🧵 below.
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Updating information regarding convergent variants BA.2.3.20, BN.1, BA.2.10.4, BN.2.1, BA.4.6.1, BQ.1, BQ.1.1.
In short, BA.2.75.2 and BQ.1.1 are the most antibody-evasive convergent variants tested, far exceeding BA.5 and approaching SARS-CoV-1 level. (1/4)
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Sharing our investigation on the unprecedented convergent RBD evolution of BA.2.75 and BA.5 on sites including 346, 356, 444-446, 450, 460, 486, which have generated highly concerning variants such as BA.2.75.2, BR.1, BJ.1, and BQ.1.1. (1/n)
biorxiv.org/content/10.110
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Sharing our investigation on the unprecedented convergent RBD evolution of BA.2.75 and BA.5 on sites including 346, 356, 444-446, 450, 460, 486, which have generated highly concerning variants such as BA.2.75.2, BR.1, BJ.1, and BQ.1.1. (1/n)
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I wanted to summarize current knowledge about origins of the #SARSCoV2 Omicron variant.
(This 🧵 doesn’t have anything new for people following topic closely, but I still get many questions about this, so am recapping current knowledge.)
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Man kann #Panorama und nicht genug danken für diesen sachlichen, unaufgeregten Bericht über grüne #Gentechnik.
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As more scientists around the world generate & share #monkeypox sequences, the international MPXV Lineage group has designated a further three lineages to help continue to classify monkeypox diversity.
nextstrain.org/monkeypox/hmpx
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Three weeks left to apply!
We at the are looking for a new colleague! Open search in the life science at assistant or associate (tenured) level.
We'd love to see applications from people with quantitative, computational, and/or theoretical approaches!
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The Biozentrum of the University of Basel in Switzerland invites applications for a tenure track assistant professorship or a tenured associate professorship.
ow.ly/scbJ50JTCTE
@biozentrum @UniBasel_en
#Biozentrum #Basel #research #science #joboffer #Professor
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We've released an updated SARS-CoV-2 dataset for Nextclade.
Newly added Pango lineages are shown in the image.
Especially the BA.2.75 sublineages (including BL.1) should be helpful.
You can check out the current tree of Pango lineages here:
nextstrain.org/nextclade/sars
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This work builds on the work of 1000s of scientists that generate SARS-CoV-2 sequence data from millions of patients around the world! Thank you very much!
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The analyses underlying the results and graphs above are simple descriptive statistics that revealed some clear patterns. But this simplicity hopefully makes interpretation easier.
We will see whether similar patterns hold in the future!
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Mutational tolerance varies strongly by gene. ORF1b and M are most conserved, while ORF3a, ORF6, ORF7ab, ORF8 are not at all. The graphs below shows distributions and the landscape of fitness costs across genes.
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As expected, 3rd positions in codons are much more tolerant to mutations than 1st and 2nd. The latter have a wide distribution with ~50% of sites more conserved than the most conserved 3rd positions (marked by vertical grey line).
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I also tried to quantify how strongly different parts of the genome are constrained by purifying selection. To do so, I counted rare mutations in each Pango lineage and used the number of lineages in which a position is polymorphic as an inverse proxy for constraint.
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I don't know. A plausible explanation could be that in D614G viruses other beneficial mutations have a smaller benefit because the virus is already very good at exploiting the cell's resources. This would be an example of diminishing returns epistasis.
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Since the synonymous rate doesn't change, this has likely more to do with selection than intrinsic mutation rate.
But surely these few early mutations didn't exhaust the supply of beneficial mutations -- we know the virus kept adapting. So why do we see this drop?
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The non-synonymous rate (blue dots) within variants was initially substantially higher (10-15/y) than it is now (~5/y). The biggest drop occurred in early 2020 and coincides with the acquisition of S:D614G and ORF1b:P314L.
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Remarkably, all variants we observed to date are compatible with a back-bone evolutionary rate of about 30 changes per year (0.001/site/year), while the within-variant rate is around 12/year (0.004/site/year).
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In this graph, each dot/square marks the emergence of a variant in time and distance from the root. The line starting at the dot shows the subsequent within variant evolution.
Non-synonymous evolution within variants is much slower than the overall rate of change.
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Within each variant, diversity and divergence increase linearly with time. The rate of synonymous evolution is around 6 changes per year in all variants, while the non-synonymous rate varies from variant to variant.
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Since its emergence in late 2019, #SARSCoV2 has diversified into multiple distinct variants.
In a new preprint, I quantify evolution within these variants and compare it to the process that gave rise to these variants.
biorxiv.org/content/10.110
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An international cohort of scientists, many of whom helped propose the new #monkeypox clade names in June, have formed a group to designate new monkeypox lineages.
Initially, 5 new lineages stemming from the B.1 ('outbreak') clade have been designated.
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