Evolutionary analysis of ZAP and its cofactors identifies intrinsically disordered regions as central elements in host-pathogen interactions.

ABSTRACT: The zinc-finger antiviral protein (ZAP) is an innate immunity sensor of non-self nucleic acids. Its antiviral activity is exerted through the physical interaction with different cofactors, including TRIM25, Riplet and KHNYN. Cellular proteins that interact with infectious agents are expected to be engaged in genetic conflicts that often result in their rapid evolution. To test this possibility and to identify the regions most strongly targeted by natural selection, we applied in silico molecular evolution tools to analyze the evolutionary history of ZAP and cofactors in four mammalian groups. We report evidence of positive selection in all genes and in most mammalian groups. On average, the intrinsically disordered regions (IDRs) embedded in the four proteins evolve significantly faster th

SUBMITTER: Cagliani R 

PROVIDER: S-EPMC11372611 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature