The activity, divergence, and evolutionary degradation of modern-day homing endonucleases and behavior of their reconstructed ancestors.

Approximately 10% of homing endonuclease genes (HEGs) encode active, well-folded proteins capable of cleaving DNA target sites, despite widespread mutations.

• Why it matters: Understanding the activity and evolution of homing endonucleases is crucial because they influence genome mobility and stability, yet many HEGs become inactivated over time, raising questions about their functional persistence.
• What they did: The study identified hundreds of novel HEGs, assessed their expression and activity, and reconstructed ancestral enzymes to analyze their stability, DNA binding, and cleavage capabilities, including a model that binds but does not cleave DNA.
• The result: Findings reveal that a minority of HEGs remain active, while ancestral reconstructions show improved stability and altered specificity, providing insights into how these enzymes evolve new functions and target sites.