Rapid Evolution of PARP Genes Suggests a Broad Role for ADP-Ribosylation in Host-Virus Conflicts

• DOI: 10.1371/journal.pgen.1004403
• Publication Date: 2014-05-29T20:25:26Z
• Authors: Matthew D. Daugherty; Janet M. Young; Julie A. Kerns; Harmit S. Malik
• Keywords: Negative selection

Post-translational protein modifications such as phosphorylation and ubiquitinylation are common molecular targets of conflict between viruses their hosts. However, the role other post-translational modifications, ADP-ribosylation, in host-virus interactions is less well characterized. ADP-ribosylation carried out by proteins encoded PARP (also called ARTD) gene family. The majority 17 human genes poorly one protein, PARP13/ZAP, has broad antiviral activity evolved under positive (diversifying) selection primates. Such evolution typical domains that locked antagonistic 'arms races' with viral factors. To identify additional may be involved interactions, we performed evolutionary analyses on all primate to search for signatures rapid evolution. Contrary expectations most 'housekeeping' functions, found nearly one-third evolving strong recurrent selection. We identified a >300 amino acid disordered region PARP4, component cytoplasmic vault structures, rapidly several mammalian lineages, suggesting this serves an important host-pathogen specificity interface. also PARP9, 14 15, only three contain both macrodomains. Macrodomains uniquely recognize, some cases can reverse, mono-ADP-ribosylation, observed throughout macro-PARP Furthermore, PARP14 PARP15 have undergone repeated rounds birth loss during vertebrate evolution, consistent innovation. Together previous studies implicated PARPs immunity, those demonstrated virally macrodomains host immune evasion, our suggest addition, recognition removal critical, underappreciated currency conflicts.