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Record W4409335107 · doi:10.1038/s44320-025-00095-4

Constraints on the optimization of gene product diversity

2025· article· en· W4409335107 on OpenAlexafffund
Daohan Jiang, Nevraj S. Kejiou, Yi Qiu, Alexander F. Palazzo, Matthew W. Pennell

Bibliographic record

VenueMolecular Systems Biology · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA regulation and disease
Canadian institutionsUniversity of Toronto
FundersNational Institute of General Medical SciencesNatural Sciences and Engineering Research Council of CanadaAgence Nationale de la Recherche
KeywordsBiologySelection (genetic algorithm)Computational biologyAdaptation (eye)GeneticsEvolutionary biologyPopulationGeneAdaptive evolutionNegative selectionPhenotypeComputer scienceGenomeMachine learning

Abstract

fetched live from OpenAlex

RNA and proteins can have diverse isoforms due to post-transcriptional and post-translational modifications. A fundamental question is whether these isoforms are mostly beneficial or the result of noisy molecular processes. To assess the plausibility of these explanations, we developed mathematical models depicting different regulatory architectures and investigated isoform evolution under multiple population genetic regimes. We found that factors beyond selection, such as effective population size and the number of cis-acting loci, significantly influence evolutionary outcomes. We found that sub-optimal phenotypes are more likely to evolve when populations are small and/or when the number of cis-loci is large. We also discovered that opposing selection on cis- and trans-acting loci can constrain adaptation, leading to a non-monotonic relationship between effective population size and optimization. More generally, our models provide a quantitative framework for developing statistical tests to analyze empirical data; as a demonstration of this, we analyzed A-to-I RNA editing levels in coleoids and found these to be largely consistent with non-adaptive explanations.

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)0.000
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: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.190
Threshold uncertainty score0.261

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
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 head0.009
GPT teacher head0.233
Teacher spread0.223 · 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

Citations2
Published2025
Admission routes2
Has abstractyes

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