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Record W2613960469 · doi:10.1101/369371

Backward evolution from gene network dynamics

2018· preprint· en· W2613960469 on OpenAlexfundno aff

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2018
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGene Regulatory Network Analysis
Canadian institutionsnot available
FundersLaufer Center for Physical and Quantitative Biology, Stony Brook UniversityDivision of Integrative Organismal SystemsNatural Sciences and Engineering Research Council of CanadaNational Institutes of HealthNational Science Foundation
KeywordsRegulatorEffectorPopulationGene regulatory networkGeneMutationMutantRegulation of gene expression

Abstract

fetched live from OpenAlex

Abstract Gene expression is controlled by regulator genes that together with effector genes form gene regulatory networks. How mutation in the genes comprising gene regulatory networks influences cell population dynamics has not been adequately investigated. In this study, we develop mathematical models to study how a mutation in a regulator gene that reaches the effector gene with a time delay affects short-term and long-term population growth. Using theory and experiment, we find a paradoxical outcome of evolution where a mutation in a regulator gene leads to an interaction between gene regulatory network and population dynamics, causing in certain cases a permanent decrease in population fitness in a constant environment. Significance Statement The properties of a cell are largely the products of its proteins, synthesized at rates depending on the regulation of protein coding genes. Single-cell measurements show that genetically identical cells can differ radically in their protein levels, partially due to the random production and degradation of proteins. It is currently unknown how mutants arise and spread in populations affected by such biological variability. We use computer simulations and evolution experiments to study how a mutant spreads in a population that carries a synthetic drug resistance gene network. Our results show for the first time a paradoxical outcome of evolution, where an initially beneficial mutation can interact with gene regulatory network dynamics and cause a permanent decrease in population fitness in the same environment.

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 categoriesMeta-epidemiology (narrow), Research integrity
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 score0.374
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0020.001
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 head0.007
GPT teacher head0.198
Teacher spread0.192 · 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.

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

Citations0
Published2018
Admission routes1
Has abstractyes

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