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Record W4362662377 · doi:10.1101/2023.04.05.535609

Neutral Drift and Threshold Selection Promote Phenotypic Variation

2023· preprint· en· W4362662377 on OpenAlexaff
Ayşe Nisan Erdoğan, Pouria Dasmeh, Raymond D. Socha, John Z. Chen, Ben Life, Rachel Jun, Linda Kiritchkov, Dan Kehila, Adrian W.R. Serohijos, Nobuhiko Tokuriki

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2023
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEvolution and Genetic Dynamics
Canadian institutionsUniversité de MontréalCanada's Michael Smith Genome Sciences CentreUniversity of British Columbia
Fundersnot available
KeywordsEvolvabilityPhenotypeBiologyPopulationGeneticsGenetic driftExperimental evolutionAdaptive evolutionAdaptation (eye)Evolutionary biologySelection (genetic algorithm)Genetic FitnessFitness landscapeNeutral mutationNeutral theory of molecular evolutionVariation (astronomy)Population sizeGeneGenetic variationMutation

Abstract

fetched live from OpenAlex

Abstract Phenotypic variations within a population exist on different scales of biological organization and play a central role in evolution by providing adaptive capacity at the population-level. Thus, the question of how evolution generates phenotypic variation within an evolving population is fundamental in evolutionary biology. Here we address this question by performing experimental evolution of an antibiotic resistance gene, VIM-2 β-lactamase, combined with diverse biochemical assays and population genetics. We found that neutral drift, i.e. , evolution under a static environment, with a low antibiotic concentration can promote and maintain significant phenotypic variation within the population with >100-fold differences in resistance strength. We developed a model based on the phenotype-environment-fitness landscape generated with >5,000 VIM-2 variants, and demonstrated that the combination of “mutation-selection balance” and “threshold-like fitness-phenotype relationship” is sufficient to explain the generation of large phenotypic variation within the evolving population. Importantly, high-resistance conferring variants can emerge during neutral drift, without being a product of adaptation. Our findings provide a novel and simple mechanistic explanation for why most genes in nature, and by extension, systems and organisms, inherently exhibit phenotypic variation, and thus, population-level evolvability.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0000.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.010
GPT teacher head0.220
Teacher spread0.210 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designSimulation or modeling
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

Citations4
Published2023
Admission routes1
Has abstractyes

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