Geometrically Encoded Positioning of Introns, Intergenic Segments, and Exons in the Human Genome

Abstract Human tissues require a mechanism to generate durable, yet modifiable, transcriptional memories to sustain cell function across a lifetime. Previously, it was demonstrated that nanoscale packing domains couple heterochromatin (cores) and euchromatin (outer zone) into unified reaction volumes that can generate transcriptional memory. In prior work, this framework demonstrates that RNA synthesis occurred within the ideal zone (intermediate density) portions of the domain. Naturally, this creates a question of where genes are positioned in relation to the packing domain architecture and which genetic material fills the domain core to sustain transcription. Here, it is proposed that this can be solved by the encoded positioning of introns, intergenic segments, and exons as a projection of the functional packing layers of domains. This suggests that introns and intergenic segments are coupled to adjacent exons to generate coherent packing domain volumes. How this organization will reconcile contradictions in epigenetic patterns, non‐randomness in oncogenic mutations, and produce durable transcriptional memory is illustrated. The study concludes by showing that this genome geometry may have coincided with the rapid evolution of body‐plan complexity, suggesting that chromatin geometry could be fundamental to metazoan evolution.