A key regulator of missing-self innate immunity is polymorphic and under diversifying selection.

Area of Science:

• Evolutionary biology
• Immunology
• Genetics

Background:

• Host-parasite co-evolution typically drives diversification in pathogen recognition genes.
• Immune genes regulating self-recognition (missing-self immunity) may be evolutionarily constrained.
• Pathogens can exploit missing-self regulators, potentially driving their diversification.

Purpose of the Study:

• To investigate the evolutionary pressures on the Complement Factor H (CFH) gene, a missing-self regulator.
• To understand how pathogen interactions shape the evolution of innate immunity in wild vertebrates.

Main Methods:

• Analyzed polymorphism and selection signatures in the bank vole CFH gene.
• Compared geographic structuring of the Borrelia-interacting CFH domain (CCP 20) with genomic markers (RAD-seq).
• Examined other innate immunity genes in the alternative complement pathway.

Main Results:

• Detected signals of positive and diversifying selection in the CFH CCP 20 domain.
• Evidence suggests CFH evolves in response to pathogen pressure from Borrelia.
• Other innate immunity genes within the alternative complement pathway also showed diversifying selection.

Conclusions:

• The innate immune sensor CFH is under diversifying selection in wild vertebrates, likely driven by pathogens.
• This study highlights the role of missing-self regulators in host-parasite co-evolution.
• Pathogen-driven selection can overcome evolutionary constraints on self-recognition genes.