Fig. 1

Irreversible genomic states at chromosomal (left) and sub-chromosomal (right) scales, their origin, and occasional function. Left: chromosomal fusion-with-mixing occurs via, e.g., Robertsonian translocation, followed by intra-chromosomal inversions. The information about the ancestral two states (two separate chromosomes) is lost after the mixing and if no plesiomorphic (outgroup) information is available. Right: similar mixing can be observed for the more functionally relevant enhancer–promoter (E–P) contacts within a single chromosome (labeled as region "A" and region "B", with E–P links shown in blue and red, respectively). E–P links are mixed via intra-chromosomal inversions and translocations within an interactive environment (mediated, e.g., through DNA loop-extrusion) making it unlikely for random inversions to disentangle them into the original state without breaking functional E–P contacts. Over longer time-scales, this entanglement may lead to the evolution of novel (green arrows) persistent E–P links. Black vertical arrows indicate possible evolutionary transitions between homologous states (two-way arrow: reversible; one-way arrow: irreversible). Slightly thicker one-way arrow for the final mixed state suggests higher level of its entropic mixing