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Securing the Language of Life: Inheritable Watermarks from DNA Language Models to Proteins
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Proposes DNAMark (synonymous-codon watermarking of DNA LM output using Evo2-embedding-driven watermark logits) and CentralMark (ESM-driven second-base watermark that is detectable in both DNA and translated protein), evaluated on a 400-sequence therapeutic DNA benchmark.
Problem
Watermarking DNA language models for biosecurity traceability is underexplored: DNA has a 4-letter alphabet, is mutated and sequenced with errors, and coding sequences must preserve protein function, so LLM watermarks such as KGW transfer poorly.
Approach
Use a trained watermark model that maps Evo2 (DNA) or ESM (protein) embeddings to watermark logits, biasing nucleotide choice; DNAMark restricts watermarks to third codon bases (synonymous, function-preserving), while CentralMark targets second codon bases so that the watermark is inherited by the translated protein's amino acid distribution.
Key results
- Under no attack, CentralMark (DNA) reaches TPR 0.875 and F1 0.928 at 1% FPR versus 0.774 TPR for the best KGW baseline (KGW-4, F1 0.868).
- Under Indels attack, DNAMark achieves F1 0.878 at 1% FPR while KGW-1 reaches 0.675, and all proposed methods keep F1 above 0.85 across attacks as claimed.
- The CRISPR-Cas9 case study designed with Evo and CentralMark reaches a TM-score of 0.6802 against wild-type SpCas9 and a z-score of 5.41.
Measured effects reported in the paper
| What was changed | Where | Measured | Effect |
|---|---|---|---|
| Use DNAMark or CentralMark instead of KGW baselines | DNA watermark detection with Evo2-7B · Therapeutic DNA under synonymous codon substitutions, nucleotide substitutions, and indels | F1 | Helped |
| Add adaptive watermark strength with EMA (ablation) | DNAMark · Therapeutic DNA watermark detection | F1 | Helped |
| Add the trained watermark model (ablation) | DNAMark · Therapeutic DNA watermark detection | F1 | Helped |
| Remove entropy guidance (ablation) | DNAMark · Generated DNA sequence quality | Sequence Identity and Degeneracy Score | Mixed |
| Remove alignment loss (ablation) | DNAMark watermark model · Therapeutic DNA watermark detection | F1 | Mixed |
| Remove normalization loss (ablation) | DNAMark watermark model · Therapeutic DNA watermark detection | F1 | Mixed |
| Increase watermark strength beyond a suitable range (ablation) | DNAMark · Generated DNA sequence | Degeneracy Score | Hurt |
| Use watermarking rather than no-watermark generation | DNAMark and CentralMark · 128-nucleotide DNA generation on Evo | generation time | Hurt |
Surprising findings
- KGW baselines reach only about 70-80% TPR on DNA versus near 100% on natural text, attributed to the four-letter vocabulary and DNA model brittleness.
- Excessive watermark strength causes DNA models to collapse into repetitive motifs such as AAAAA.
Limitations
- Relies on green/red list partitioning, which the authors note should be replaced by schemes independent of green/red lists.
- Indels and nucleotide substitutions degrade detection (e.g., CentralMark TPR near 76% under Indels at 1% FPR).
- No wet-lab validation of the watermarked sequences.
Experimental setup
Datasets: RefGen human coding sequences NCBI RefSeq UniProt secondary structure annotations
Benchmarks: Therapeutic DNA benchmark (400 sequences)
Metrics: TPR at 1% FPR TPR at 10% FPR F1 sequence identity degeneracy score generation time TM-score
Baselines: KGW-1 KGW-2 KGW-4
Builds on: KGW watermark Evo2 ESM SIR
Closest papers by meaning
- BEND: Benchmarking DNA Language Models on Biologically Meaningful Tasks (ICLR 2024 · similarity 0.84)
- LEMON-ZEST: Evolution-Informed Tokenization for Efficient Protein Language Modeling (NeurIPS 2026 · similarity 0.83)
- DART-Eval: A Comprehensive DNA Language Model Evaluation Benchmark on Regulatory DNA (NeurIPS 2024 · similarity 0.83)
- Steering Protein Language Models (ICML 2025 · similarity 0.83)
- Break the Trade-off Between Watermark Strength and Speculative Sampling Efficiency for Language Models (ICLR 2026 · similarity 0.83)
- A Watermark for Order-Agnostic Language Models (ICLR 2025 · similarity 0.82)
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