A novel surfactant protein is associated with extrapulmonary respiration in lungless salamanders

Abstract Numerous physiological and morphological adaptations were achieved during the transition to lungless respiration following evolutionary lung loss in plethodontid salamanders, including those that enable efficient gas exchange across extrapulmonary tissue. However, the molecular basis of these adaptations is unknown. Here we show that lungless salamanders express in the skin and buccal cavity—the principal sites of respiratory gas exchange in these species—a novel paralog of the gene Surfactant-Associated Protein C (SFTPC), which is a critical component of pulmonary surfactant expressed exclusively in the lung in other vertebrates. The paralogous gene appears to be found only in salamanders, but, similar to SFTPC, in lunged salamanders it is expressed only in the lung. This heterotopic gene expression, combined with predictions from structural modeling and respiratory tissue ultrastructure, suggest that lungless salamanders produce pulmonary surfactant-like secretions outside the lungs and that the novel paralog of SFTPC might facilitate extrapulmonary respiration in the absence of lungs. Heterotopic expression of the SFTPC paralog may have contributed to the remarkable evolutionary radiation of lungless salamanders, which account for more than two thirds of urodele species alive today.