Two harmful gene variants can restore function when combined, study reveals
Pacific Northwest Research Institute (PNRI) researchers have shown that two harmful genetic variants can restore normal function when present together, experimentally validating a decades-old hypothesis proposed by Francis Crick.
The study, conducted in collaboration with scientists from George Mason University, demonstrated this effect in the enzyme argininosuccinate lyase (ASL), where variant combinations that were nonfunctional on their own regained activity when paired. PNRI researcher Aimée Dudley’s lab measured thousands of variant combinations, while George Mason University researchers applied an AI-driven model that achieved high accuracy in predicting functional recovery and successfully transferred predictions to a related enzyme.
The findings highlight the Pacific Northwest’s role in translating genomic research using artificial intelligence to advance precision medicine.
Photo Credit: George Mason University