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Nature· 2026Q1

Genome modelling and design across all domains of life with Evo 2

Garyk Brixi, Matthew G. Durrant, Jerome Ku, Mohsen Naghipourfar et al.

Short summary

Evo 2, a new AI foundation model trained on 9 trillion DNA base pairs, accurately predicts the functional impacts of genetic variations and generates novel genomic sequences across all domains of life with single-nucleotide resolution and a 1 million token context window.

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Key points

  • Evo 2 is an AI foundation model trained on 9 trillion DNA base pairs across all domains of life.
  • It features a 1 million token context window with single-nucleotide resolution.
  • Evo 2 accurately predicts functional impacts of genetic variations without fine-tuning.
  • The model generates coherent and natural-sounding mitochondrial, prokaryotic, and eukaryotic sequences.
  • Evo 2 learns representations associated with key biological features like transcription factor binding sites and protein structural elements.

AI-generated from the title and abstract; the full text is not read.

Abstract

All of life encodes information with DNA. Although tools for genome sequencing, synthesis and editing have transformed biological research, we still lack sufficient understanding of the immense complexity encoded by genomes to predict the effects of many classes of genomic changes or to intelligently compose new biological systems. Artificial intelligence models that learn information from genomic sequences across diverse organisms have increasingly advanced prediction and design capabilities1,2. Here we introduce Evo 2, a biological foundation model trained on 9 trillion DNA base pairs from a highly curated genomic atlas spanning all domains of life to have a 1 million token context window with single-nucleotide resolution. Evo 2 learns to accurately predict the functional impacts of genetic variation—from noncoding pathogenic mutations to clinically significant BRCA1 variants—without task-specific fine-tuning. Mechanistic interpretability analyses reveal that Evo 2 learns representations associated with biological features, including exon–intron boundaries, transcription factor binding sites, protein structural elements and prophage genomic regions. The generative abilities of Evo 2 produce mitochondrial, prokaryotic and eukaryotic sequences at genome scale with greater naturalness and coherence than previous methods. Evo 2 also generates experimentally validated chromatin accessibility patterns when guided by predictive models3,4 and inference-time search. We have made Evo 2 fully open, including model parameters, training code5, inference code and the OpenGenome2 dataset, to accelerate the exploration and design of biological complexity. Evo 2 is an artificial intelligence-based biological foundation model trained on 9 trillion DNA base pairs spanning all domains of life that predicts functional properties from genomic sequences and provides a rich generative model for researchers in biology.

The authors' abstract, as published at the source. Nature, 2026 · DOI ↗

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Field: Molecular Biology

Molecular BiologyBiochemistry, Genetics and Molecular Biology