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Record W2141846102 · doi:10.1073/pnas.1115620109

Escape from Adaptive Conflict follows from weak functional trade-offs and mutational robustness

2012· article· en· W2141846102 on OpenAlexafffund
Tobias Sikosek, Hue Sun Chan, Erich Bornberg‐Bauer

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2012
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEvolution and Genetic Dynamics
Canadian institutionsUniversity of Toronto
FundersCanadian Institutes of Health Research
KeywordsNeofunctionalizationSubfunctionalizationFunctional divergenceGene duplicationRobustness (evolution)BiologyEvolvabilityAdaptive evolutionGeneGene dosageComputational biologyAdaptation (eye)GeneticsGene familyGenomeNeuroscienceGene expression

Abstract

fetched live from OpenAlex

A fundamental question in molecular evolution is how proteins can adapt to new functions while being conserved for an existing function at the same time. Several theoretical models have been put forward to explain this apparent paradox. The most popular models include neofunctionalization, subfunctionalization (SUBF) by degenerative mutations, and dosage models. All of these models focus on adaptation after gene duplication. A newly proposed model named "Escape from Adaptive Conflict" (EAC) includes adaptive processes before and after gene duplication that lead to multifunctional proteins, and divergence (SUBF). Support for the importance of multifunctionality for the evolution of new protein functions comes from two experimental observations. First, many enzymes have highly evolvable promiscuous side activities. Second, different structural states of the same protein can be associated with different functions. How these observations may be related to the EAC model, under which conditions EAC is possible, and how the different models relate to each other is still unclear. Here, we present a theoretical framework that uses biophysical principles to infer the roles of functional promiscuity, gene dosage, gene duplication, point mutations, and selection pressures in the evolution of proteins. We find that selection pressures can determine whether neofunctionalization or SUBF is the more likely evolutionary process. Multifunctional proteins, arising during EAC evolution, allow rapid adaptation independent of gene duplication. This becomes a crucial advantage when gene duplications are rare. Finally, we propose that an increase in mutational robustness, not necessarily functional optimization, can be the sole driving force behind SUBF.

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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.831
Threshold uncertainty score0.274

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 studies0.0000.001
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 head0.035
GPT teacher head0.274
Teacher spread0.240 · 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

Citations65
Published2012
Admission routes2
Has abstractyes

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