The study investigates the genome evolution of hagfish, a jawless fish, to understand early vertebrate evolution. Using a chromosome-scale genome sequence of the brown hagfish *Eptatretus atami*, the researchers identify and date key polyploidization events in vertebrate evolution, including an auto-tetraploidization (IR) before the Cambrian split between cyclostomes and gnathostomes, and allo-tetraploidizations (2R) in gnathostomes and cyclostomes. Hagfish have undergone extensive genomic changes, including chromosomal fusions and gene losses essential for organ systems, leading to their simplified body plan. The study also characterizes programmed DNA elimination in hagfish, identifying germline-specific genes and repetitive elements that are deleted during early development. These findings provide insights into the evolution of vertebrate germline-specific chromosomes and the resolution of genetic conflicts between somatic and germline cells. The analysis of Hox clusters and neural crest-related genes suggests that the neural crest originated before the IR event, and that subfunctionalization played a limited role in the emergence of other vertebrate novelties like limbs. The study highlights the unique evolutionary path of cyclostomes and the extensive gene loss in hagfish, contributing to their morphological simplification.The study investigates the genome evolution of hagfish, a jawless fish, to understand early vertebrate evolution. Using a chromosome-scale genome sequence of the brown hagfish *Eptatretus atami*, the researchers identify and date key polyploidization events in vertebrate evolution, including an auto-tetraploidization (IR) before the Cambrian split between cyclostomes and gnathostomes, and allo-tetraploidizations (2R) in gnathostomes and cyclostomes. Hagfish have undergone extensive genomic changes, including chromosomal fusions and gene losses essential for organ systems, leading to their simplified body plan. The study also characterizes programmed DNA elimination in hagfish, identifying germline-specific genes and repetitive elements that are deleted during early development. These findings provide insights into the evolution of vertebrate germline-specific chromosomes and the resolution of genetic conflicts between somatic and germline cells. The analysis of Hox clusters and neural crest-related genes suggests that the neural crest originated before the IR event, and that subfunctionalization played a limited role in the emergence of other vertebrate novelties like limbs. The study highlights the unique evolutionary path of cyclostomes and the extensive gene loss in hagfish, contributing to their morphological simplification.