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Record W4407203673 · doi:10.1016/j.sbi.2025.102996

A building blocks perspective on protein emergence and evolution

2025· review· en· W4407203673 on OpenAlexfundno aff
Yishi Ezerzer, Moran Frenkel‐Pinter, Rachel Kolodny, Nir Ben‐Tal

Bibliographic record

VenueCurrent Opinion in Structural Biology · 2025
Typereview
Languageen
FieldPhysics and Astronomy
TopicOrigins and Evolution of Life
Canadian institutionsnot available
FundersTel Aviv UniversityAzrieli FoundationIsrael Science FoundationMinerva FoundationFederation of European Biochemical Societies
KeywordsPerspective (graphical)Protein evolutionEvolutionary biologyComputational biologyBiologyData scienceComputer scienceGeneticsArtificial intelligenceGene

Abstract

fetched live from OpenAlex

Recent findings increasingly suggest the emergence of proteins by mix and match of short peptides, or ‘building blocks’. What are these building blocks, and how did they evolve into contemporary proteins? We review two complementary approaches to tackling these questions. First, a bottom-up approach that involves identifying putative components of primordial peptides, and the synthetic routes through which these peptides may have emerged. Second, searches in protein space to reveal building blocks that make up the contemporary protein repertoire; proteins that are not closely related to one another may nevertheless have certain parts in common, suggesting common ancestry. Identifying such shared building blocks, and characterizing their functions, can shed light on the ancient molecules from which proteins emerged, and hint at the mechanisms that govern their evolution. A key challenge lies in merging these two approaches to create a cohesive narrative of how proteins emerged and continue to evolve. • Proteins evolved from smaller ‘building blocks’ of various sizes. • Prebiotic studies suggest building blocks based on chemical considerations. • Prebiotic peptides could have been more diverse than polypeptides. • Computational analysis of protein space suggests building blocks. • To form a protein the building blocks should fit geometrically and dynamically.

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 categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.952
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
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 head0.044
GPT teacher head0.409
Teacher spread0.366 · 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 designNot applicable
Domainnot available
GenreReview

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

Citations5
Published2025
Admission routes1
Has abstractyes

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