Rapid evolution of a primate-restricted inflammasome regulator (43.25)

Abstract

Abstract Pyrin-only protein 2 (POP2) is a small protein consisting solely of a pyrin domain capable of inhibiting IL-1β processing by preventing inflammasome assembly. Comparative genomic analysis reveals that POP2 is absent from the genomes of not only mice and rats, but those of other domestic mammals and new world monkeys as well. However, POP2 is present in the genomes of those primate species most closely related to humans. Interestingly, chimpanzee POP2 is identical to human POP2 at both the DNA and protein level but macaque POP2, although highly conserved, is not. Our analysis demonstrates that POP2 arose rapidly and recently in the mammalian genome and is likely derived from duplication and contraction of an extant NLR gene. Our findings support the hypothesis that mammalian NLR loci involved in innate and adaptive immunity as well as mammalian development, have been subject to recent and strong selective pressures driving their evolution. As POP2 is capable of regulating processes linked to innate immunity and inflammation, its highly restricted and conserved presence in the genomes of Old World primates suggests that further regulation of these events was critical in primate evolution.