Evidence map›Paper›PMID 38615031›Full record

ArticleNature communications2024

Positive selection underlies repeated knockout of ORF8 in SARS-CoV-2 evolution.

Cassia Wagner, Kathryn E Kistler, Garrett A Perchetti, Noah Baker, Lauren A Frisbie, Laura Marcela Torres, Frank Aragona, Cory Yun, Marlin Figgins, Alexander L Greninger and 4 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
9.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 24 citations in OpenAlex.

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  15. Ciprofloxacin-driven purifying selection on viral genomes accelerates soil NProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  16. The Recurring Loss of ORF8 Secretion in Dominant SARS-CoV-2 Variants.International journal of molecular sciences · 2025
    Article
  17. Automated annotation and validation of human respiratory virus sequences using VADR.Database : the journal of biological databases and curation · 2025
    Article
  18. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 2 countries.

Cassia WagnerDepartment of Genome Sciences, University of Washington, Seattle, WA, USA. cassiasw@uw.edu.ORCID http://orcid.org/0000-0002-9934-7578
Kathryn E KistlerVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-3216-0020
Garrett A PerchettiDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0003-3786-0509
Noah BakerDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-6368-2083
Lauren A FrisbieWashington State Department of Health, Shoreline, WA, USA.ORCID http://orcid.org/0000-0002-4267-8448
Laura Marcela TorresWashington State Department of Health, Shoreline, WA, USA.ORCID http://orcid.org/0000-0001-9496-0595
Frank AragonaWashington State Department of Health, Shoreline, WA, USA.
Cory YunWashington State Department of Health, Shoreline, WA, USA.
Marlin FigginsVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-0686-0816
Alexander L GreningerVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-7443-0527
Alex CoxWashington State Department of Health, Shoreline, WA, USA.
Hanna N OlteanWashington State Department of Health, Shoreline, WA, USA.
Pavitra RoychoudhuryVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-4567-8232
Trevor BedfordVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Washington State Department of Health · USUniversity of Washington · USHoward Hughes Medical Institute · USCape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa · ZAFred Hutch Cancer Center · US

Funding

University of Washington Medical Scientist Training Program: MD/PhDT32GM007266 · NIGMS · UNIVERSITY OF WASHINGTON · PI HORWITZ, MARSHALL S. · 1985 to 2023
$30.4M
High-Performance Compute Cluster for Comprehensive Cancer and Infectious Diseases ResearchS10OD028685 · OD · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BRADLEY, PHILIP · 2020 to 2020
$2.0M
FHCRC High-Performance Computing ClusterS10OD020069 · OD · FRED HUTCHINSON CANCER RESEARCH CENTER · PI KOOPERBERG, CHARLES L · 2015 to 2015
$600k
NIGMS NIH HHS T32 GM007266NIH HHS S10 OD020069NIH HHS S10 OD028685
6 · The paper itself

Abstract

Knockout of the ORF8 protein has repeatedly spread through the global viral population during SARS-CoV-2 evolution. Here we use both regional and global pathogen sequencing to explore the selection pressures underlying its loss. In Washington State, we identified transmission clusters with ORF8 knockout throughout SARS-CoV-2 evolution, not just on novel, high fitness viral backbones. Indeed, ORF8 is truncated more frequently and knockouts circulate for longer than for any other gene. Using a global phylogeny, we find evidence of positive selection to explain this phenomenon: nonsense mutations resulting in shortened protein products occur more frequently and are associated with faster clade growth rates than synonymous mutations in ORF8. Loss of ORF8 is also associated with reduced clinical severity, highlighting the diverse clinical impacts of SARS-CoV-2 evolution.

Indexed as

COVID-19SARS-CoV-2Selection, GeneticHumansPhylogenyViral ProteinsORF8 protein, SARS-CoV-2Viral Proteins

Identifiers

PMID38615031
PMCPMC11016114
OpenAlexW4394783534

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.