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Record W4407309548 · doi:10.1073/pnas.2413675122

Giant RNA genomes: Roles of host, translation elongation, genome architecture, and proteome in nidoviruses

2025· article· en· W4407309548 on OpenAlexaff
Benjamin W. Neuman, Alexandria Smart, Orian Gilmer, Redmond P. Smyth, Josef Vaas, Nicolai Böker, Dmitry V. Samborskiy, Ralf Bartenschlager, Stefan Seitz, Alexander E. Gorbalenya, Neva Caliskan, Chris Lauber

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2025
Typearticle
Languageen
FieldAgricultural and Biological Sciences
TopicAnimal Virus Infections Studies
Canadian institutionsInnovation Cluster (Canada)
FundersHelmholtz AssociationUniversität RegensburgMedizinischen Hochschule HannoverEuropean Research CouncilUniversiteit LeidenLeids Universitair Medisch CentrumLomonosov Moscow State UniversityUniversité de StrasbourgDeutsche ForschungsgemeinschaftDeutsches Krebsforschungszentrum
KeywordsBiologyGenomeGeneticsRNAGenomic organizationRNA virusGene

Abstract

fetched live from OpenAlex

have the largest known RNA genomes of vertebrate and invertebrate viruses with 36.7 and 41.1 kb, respectively. The acquisition of a proofreading exoribonuclease (ExoN) by an ancestral nidovirus enabled crossing of the 20 kb barrier. Other factors constraining genome size variations in nidoviruses remain poorly defined. We assemble 76 genome sequences of invertebrate nidoviruses from >500.000 published transcriptome experiments and triple the number of known nidoviruses with >36 kb genomes, including a 64 kb RNA genome. Many of the identified viral lineages acquired putative enzymatic and other protein domains linked to genome size, host phyla, or virus families. The inserted domains may regulate viral replication and virion formation, or modulate infection otherwise. We classify ExoN-encoding nidoviruses into seven groups and four subgroups, according to canonical and noncanonical modes of viral replicase expression by ribosomes and genomic organization (reModes). The most-represented group employing the canonical reMode comprises invertebrate and vertebrate nidoviruses, including coronaviruses. Six groups with noncanonical reModes include invertebrate nidoviruses with 31-to-64 kb genomes. Among them are viruses with segmented genomes and viruses utilizing dual ribosomal frameshifting that we validate experimentally. Moreover, largest polyprotein length and genome size in nidoviruses show reMode- and host phylum-dependent relationships. We hypothesize that the polyprotein length increase in nidoviruses may be limited by the host-inherent translation fidelity, ultimately setting a nidovirus genome size limit. Thus, expansion of ExoN-encoding RNA virus genomes, the vertebrate/invertebrate host division, the control of viral replicase expression, and translation fidelity are interconnected.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.804
Threshold uncertainty score0.245

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.042
GPT teacher head0.277
Teacher spread0.235 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations16
Published2025
Admission routes1
Has abstractyes

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