PathfinderSNT: An Operator-Constrained Framework for Phase Transitions Between ORF Conservation and De Novo Expansion

We present PathfinderSNT (Sequence Nucleotide Tracker), a constraint-driven genome reorganization framework whose central empirical finding is phase-dependent behaviour: the same operator system operates in a conservation regime on high-density sequences, suppressing spurious open reading frame (ORF) inflation, and exhibits an expansion trend on low-density sequences, actively installing new coding structure. This behaviour emerges automatically from the interaction of two orthogonal mechanisms: the ΠORF disjoint projection invariant, which prevents representation-level metric inflation, and the frozen soft-clamp, a density-adaptive feedback controller that ensures probability-preserving operator consistency at every reorganisation cycle. The framework models genome reorganisation as a seven-operator dynamical system {∧=, ⟲=, ↗=, ⟲r, ∞/, □/, ⋄+} implementing a coupled diagnose–measure–delete–fill pipeline governed by a Markov operator semigroup. We validate on six real genomic sequences spanning bacterial chromosomes, a bacteriophage, a cloning plasmid, and vertebrate mitochondrial DNA: E. coli K-12 MG1655, Prochlorococcus marinus MIT 9313, Mycoplasmoides genitalium M2288, pUC19, Lambda phage, and the complete human mitochondrial genome (NC 012920). Across N = 10 independent seeds (N = 5 for the human mitochondrial genome) and 30 reorganisation cycles, the framework significantly suppresses ORF-count inflation relative to random mutation on all five high-density genomes (Δ = −3.0 to −26.6, pboot = 1.000), including the human mitochondrial genome analysed under the vertebrate mitochondrial genetic code. On the low-density pUC19 plasmid, an expansion trend was observed (Δ = +0.4) that did not reach statistical significance (pboot = 0.195). Critically, 45% of framework-inserted ORFs across all six organisms (33/74) returned significant BLAST hits (E < 0.01) against UniProtKB/Swiss-Prot, including humanin-like peptides and core respiratory-chain subunits in human mitochondrial DNA, indicating that the framework operates de novo—without reference to existing annotations—yet preferentially installs biologically plausible coding structure rather than statistical noise.

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Publication Details

Journal
Zenodo (CERN European Organization for Nuclear Research)
Published
2026-08-25
DOI
https://doi.org/10.5281/zenodo.22094665
Primary Topic
Bacterial Genetics and Biotechnology
Type
preprint
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preprint

PathfinderSNT: An Operator-Constrained Framework for Phase Transitions Between ORF Conservation and De Novo Expansion

Durhan Yazır
Zenodo (CERN European Organization for Nuclear Research)
Bacterial Genetics and Biotechnology
preprint

PathfinderSNT: An Operator-Constrained Framework for Phase Transitions Between ORF Conservation and De Novo Expansion

Durhan Yazır
preprint en

Abstract

We present PathfinderSNT (Sequence Nucleotide Tracker), a constraint-driven genome reorganization framework whose central empirical finding is phase-dependent behaviour: the same operator system operates in a conservation regime on high-density sequences, suppressing spurious open reading frame (ORF) inflation, and exhibits an expansion trend on low-density sequences, actively installing new coding structure. This behaviour emerges automatically from the interaction of two orthogonal mechanisms: the ΠORF disjoint projection invariant, which prevents representation-level metric inflation, and the frozen soft-clamp, a density-adaptive feedback controller that ensures probability-preserving operator consistency at every reorganisation cycle. The framework models genome reorganisation as a seven-operator dynamical system {∧=, ⟲=, ↗=, ⟲r, ∞/, □/, ⋄+} implementing a coupled diagnose–measure–delete–fill pipeline governed by a Markov operator semigroup. We validate on six real genomic sequences spanning bacterial chromosomes, a bacteriophage, a cloning plasmid, and vertebrate mitochondrial DNA: E. coli K-12 MG1655, Prochlorococcus marinus MIT 9313, Mycoplasmoides genitalium M2288, pUC19, Lambda phage, and the complete human mitochondrial genome (NC 012920). Across N = 10 independent seeds (N = 5 for the human mitochondrial genome) and 30 reorganisation cycles, the framework significantly suppresses ORF-count inflation relative to random mutation on all five high-density genomes (Δ = −3.0 to −26.6, pboot = 1.000), including the human mitochondrial genome analysed under the vertebrate mitochondrial genetic code. On the low-density pUC19 plasmid, an expansion trend was observed (Δ = +0.4) that did not reach statistical significance (pboot = 0.195). Critically, 45% of framework-inserted ORFs across all six organisms (33/74) returned significant BLAST hits (E < 0.01) against UniProtKB/Swiss-Prot, including humanin-like peptides and core respiratory-chain subunits in human mitochondrial DNA, indicating that the framework operates de novo—without reference to existing annotations—yet preferentially installs biologically plausible coding structure rather than statistical noise.

Zenodo (CERN European Organization for Nuclear Research)
IR Dynamics (United States) (US)
Life in Land
Bacterial Genetics and Biotechnology
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