Genomic rearrangements rewire chromatin contacts and drive adaptive gene expression divergence in mammals

Genomic rearrangements (GRs) are pervasive in mammalian evolution, yet their contribution to adaptive trait divergence remains poorly defined. By examining 71 mammalian genomes across eight major clades, we uncovered 206 clade-specific disruptions of ancestral synteny. These rearrangements consistently localize near genes underpinning clade-specific physiological, metabolic and behavioural traits and coincided with the accelerated expression rates in the affected lineage. The disruption of otherwise syntenic chromatin contacts and the fusion of domains with contrasting epigenetic states implied that the alteration in regulatory adjacency may underlie the expression divergence. Primate-specific rearrangements exhibited signatures of selective constraint, including fixation across species, reduced recombination, elevated linkage disequilibrium, and enhanced co-expression of genes flanking rearranged loci, indicating that these genomic architectures are selectively maintained. Our observations imply that the clade-specific genomic rearrangements repeatedly reconfigured the mammalian regulatory landscape and likely served as an evolutionary substrate for lineage-specific adaptation.