Abstract

The immune system must distinguish between its own cells and invading pathogens. While the immune regulators involved in self-recognition are expected to be evolutionarily stable because of their function, many pathogens, including Borrelia - the causing agent of Lyme disease, exploit them to evade immune clearance, potentially driving their diversification. How these opposing selective pressures shape the evolution of immune genes is still unclear. We tested these competing hypotheses by studying the Complement Factor H (CFH), a key regulator of innate immunity, in wild populations of bank voles, a major reservoir host for Borrelia. We found evidence of positive and diversifying selection in the region of CFH that contains binding sites for both host molecules and Borrelia virulence factors. These findings demonstrate that a key regulator of innate immunity is under strong selection, likely driven by pathogens.