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

Garyk Brixi, Matthew G. Durrant, Jerome Ku, Mohsen Naghipourfar, Michael Poli, Gwanggyu Sun et al. · 2026 · 147 citationsRead the paper

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.

What the full text shows

Working prototype
  • Experimental validation of de novo designed multi-kilobase DNA sequences with specified chromatin accessibility patterns. — AUROCs of 0.92–0.95 (Synthesized DNA integrated into mouse embryonic stem cells (mESCs) and measured via ATAC-seq)
  • Zero-shot prediction of non-SNV coding and noncoding variants (insertions/deletions). — Outperformed all other tested models (Human clinical and experimentally determined variants)
  • Zero-shot prediction of noncoding SNVs in the BRCA1 gene. — Outperformed all other tested models, including supervised splicing predictors (BRCA1 noncoding variants near or far from splice sites)
  • Identification of latent representations (features) corresponding to biological elements without explicit labels. (Sparse autoencoders (SAEs) trained on Evo 2 representations from layer 26)
  • Retrieval of specific sequences within a large genomic context. — 100 bp sequence within 1 million bp (Synthetic 'needle-in-a-haystack' evaluation)
  • Throughput improvement over Transformer baselines. — Up to 3x speedup (40B parameter model at 1 million context length)
Setup
Trained on OpenGenome2 dataset (9.3 trillion tokens for 40B model, 2.4 trillion for 7B model) spanning bacteria, archaea, eukarya, and bacteriophage.
How
The researchers developed Evo 2, a biological foundation model using a StripedHyena 2 convolutional multi-hybrid architecture. They employed a two-phase training process (short-context pretraining followed by long-context midtraining) and used beam search with inference-time guidance from Enformer and Borzoi models for sequence design.
Limitations
Generative evaluations do not guarantee that sequences will function in cells. · Inference-time guidance for high-quality generation is computationally intensive. · Performance on human viruses was intentionally weakened for biosafety (data exclusion).

Summarized by Gemma 4 from the open-access full text · 10 Oct 2026. Read it