Giant genome of the vampire squid reveals the derived state of modern octopod karyotypes

Ancient evolutionary transitions in animal chromosomal complements and their phenotypic impacts remain understudied. Few systems exist where these events can be dissected into individual steps. In coleoid cephalopods (octopus, squid, cuttlefish), an ancient coleoid chromosomal rearrangement event (ACCRE) resulted in a substantial increase in the chromosome number. However, the discrepancies between extant octopodiform (octopus, ∼30 chromosomes) and decapodiform (squid and cuttlefish, ∼46 chromosomes) karyotypes and the direction of this transition remain unexplained. Through sequencing of the basally branching octopodiform, the vampire squid <i>Vampyroteuthis</i> sp., we reveal its partial retention of the decapodiform karyotype. Together with the chromosome-level assembly of the pelagic octopod <i>Argonauta hians</i>, we show that modern octopod genomes were extensively shaped by chromosomal fusion-with-mixing followed by inter-chromosomal translocations. These irreversible processes have resulted in a more entangled genomic configuration in octopods. Our results offer broader insights into general patterns of chromosomal evolution following large-scale rearrangement in animal genomes.