Lungfish comparative genomics reveals ancient gene networks co-opted for life on land

Abstract The transition from water to land was a defining event in vertebrate evolution, requiring major changes in physiology and gene regulation. Lungfish, the closest extant relatives of tetrapods, offer a unique window into this process through their capacity for estivation, a physiological state that mirrors key demands of terrestrial life. Here, we constructed and compared gene co-expression networks across five vertebrate species using multi-tissue transcriptomic data. Focusing on estivating lungfish tissues, we identified conserved modules enriched in core functions, including metabolic regulation, RNA processing, and protein turnover. We further show that a subset of retained ohnologs from the vertebrate 2R-WGD act as network hubs under directional selection in key phylogenetic branches. These genes, involved in membrane trafficking, cytoskeletal regulation, water balance, and stress response, illustrate how duplicated, dosage-sensitive genes were co-opted to meet the physiological demands of terrestrial adaptation. Together, our findings support a model in which ancient whole-genome duplications supplied raw material later shaped by selection and network rewiring to enable extreme physiological adaptations such as estivation. Teaser Ancient duplicated gene networks in lungfish estivation reveal how vertebrates repurposed genomic toolkits to adapt to land. Competing Interest Statement The authors have declared no competing interest.