A possible mechanism for maintenance of the deleterious allele of human CASPASE-12

In humans, a functional CASPASE-12 (CASP12) gene has been identified only in persons of African heritage and has been suggested to play a regulatory role in response to bacterial pathogens and in promoting and increased susceptibility to sepsis. The existence of a gene whose effect is deleterious, and which has been the subject of extensive negative selection in the rest of the human population, implies the simultaneous presence of some selective benefit for persons having CASP12. Given the importance of inflammatory immune responses in controlling the initial stages of infection, and the role that CASP12 plays in down-regulating inflammation, we hypothesize that pathogens which exploit the inflammatory response are restrained by an active CASP12 gene product. Several candidate pathogens are discussed.