Flipons enable genomes to learn by intermediating the exchange of energy for information.

Recent findings have confirmed the long-held belief that alternative DNA conformations encoded by genetic elements called flipons have important biological roles. Many of these alternative structures are formed by sequences originally spread throughout the human genome by endogenous retroelements (ERE) that captured 50% of the territory before being disarmed. Only 2.6% of the remaining DNA codes for proteins. Other organisms have instead streamlined their genomes by eliminating invasive retroelements and other repeat elements. The question arises, why retain any ERE at all? A new synthesis suggests that flipons enable genomes to learn and programme the context-specific readout of information by altering the transcripts produced. The exchange of energy for information is mediated through changes in DNA topology. Here I provide a formulation for how genomes learn and describe the underlying p-bit algorithm through which flipons are tuned. The framework suggests new strategies for the therapeutic reprogramming of cells.