Primary regulatory T cell activator FOXP3 is present across Amphibia.

The overall structure of the immune system is highly conserved across jawed vertebrates, but characterization and description of the immune system is heavily biased toward mammals. One arm of the vertebrate immune system, the adaptive immune system, mounts pathogen-specific responses that tend to be robust and effective at clearing pathogens. This system requires selection against self-recognition and modulation of the immune response. One of the mechanisms of immune modulation is the presence of regulatory T cells that suppress other effector immune cells. Regulatory T cells and their primary activator forkhead box protein P3 (FOXP3) have been well characterized in mammalian models but unexplored in most other vertebrate taxa. Amphibians are a good focal group for the characterization of FOXP3 due to their phylogenetic position on the vertebrate tree of life, and their susceptibility to emerging pathogens. In this study, we mined available transcriptomic and genomic data to confirm the presence of FOXP3 across the amphibian tree of life. We find that FOXP3 is present in all major clades of amphibians. We also test whether selection on FOXP3 shows signatures of intensification among the three main clades of amphibians, which may reflect shifts in the stringency of natural selection on this gene. Our findings provide insights into the evolutionary history of the vertebrate immune system and confirm the conservation of vertebrate immune genes within amphibians.