Topological mixing and irreversibility in animal chromosome evolution

Animal chromosome homology can persist over hundreds of millions of years, despite fusions and translocations. The frequency, pace, and impact of these changes remain unclear. We develop a multiscale manifold representation of pan-animal genome homology to compare 5821 chromosome-scale genomes across 19 phyla and 4454 species. This “evolutionary genome topology” approach simultaneously captures chromosomal and subchromosomal organization. We find that while all 406 pairwise fusions of 29 ancestral animal linkage groups have been sampled by metazoan genome diversity, the full combinatorial potential within chromosomes remains far from explored. Our approach shows that irreversible genomic changes, caused in particular by chromosomal consolidation, dissociation, and fusion-with-mixing, place clades in distinct regions of genome architecture space. Progressive accumulation of these mixed states across genomic scales contributes to the diverging paths of animal genome evolution and has a long-lasting impact on a broad range of genes, including key developmental loci.