The researchers argue that this setup lets Evo “link nucleotide-level patterns to kilobase-scale genomic context.” In other words, if you prompt it with a large chunk of genomic DNA, Evo can interpret that as an LLM would interpret a query and produce an output that, in a genomic sense, is appropriate for that interpretation.

The researchers reasoned that, given the training on bacterial genomes, they could use a known gene as a prompt, and Evo should produce an output that includes regions that encode proteins with related functions. The key question is whether it would simply output the sequences for proteins we know about already, or whether it would come up with output that’s less predictable.

Novel proteins

To start testing the system, the researchers prompted it with fragments of the genes for known proteins and determined whether Evo could complete them. In one example, if given 30 percent of the sequence of a gene for a known protein, Evo was able to output 85 percent of the rest. When prompted with 80 percent of the sequence, it could return all of the missing sequence. When a single gene was deleted from a functional cluster, Evo could also correctly identify and restore the missing gene.

The large amount of training data also ensured that Evo correctly identified the most important regions of the protein. If it made changes to the sequence, they typically resided in the areas of the protein where variability is tolerated. In other words, its training had enabled the system to incorporate the rules of evolutionary limits on changes in known genes.

So, the researchers decided to test what happened when Evo was asked to output something new. To do so, they used bacterial toxins, which are typically encoded along with an anti-toxin that keeps the cell from killing itself whenever it activates the genes. There are a lot of examples of these out there, and they tend to evolve rapidly as part of an arms race between bacteria and their competitors. So, the team developed a toxin that was only mildly related to known ones, and had no known antitoxin, and fed its sequence to Evo as a prompt. And this time, they filtered out any responses that looked similar to known antitoxin genes.