title: A Wolbachia deubiquitylating enzyme induces cytoplasmic incompatibility.
abstract: Wolbachia are obligate intracellular bacteria1that infect arthropods, including approximately two-thirds of insect species2. Wolbachia manipulate insect reproduction by enhancing their inheritance through the female germline. The most common alteration is cytoplasmic incompatibility (CI)3-5, where eggs from uninfected females fail to develop when fertilized by sperm from Wolbachia-infected males. By contrast, if female and male partners are both infected, embryos are viable. CI is a gene-drive mechanism impacting population structure6and causing reproductive isolation7, but its molecular mechanism has remained unknown. We show that a Wolbachia deubiquitylating enzyme (DUB) induces CI. The CI-inducing DUB, CidB, cleaves ubiquitin from substrates and is encoded in a two-gene operon, and the other protein, CidA, binds CidB. Binding is strongest between cognate partners in cidA-cidB homologues. In transgenic Drosophila, the cidA-cidB operon mimics CI when sperm introduce it into eggs, and a catalytically inactive DUB does not induce sterility. Toxicity is recapitulated in yeast by CidB alone; this requires DUB activity but is rescued by coexpressed CidA. A paralogous operon involves a putative nuclease (CinB) rather than a DUB. Analogous binding, toxicity and rescue in yeast were observed. These results identify a CI mechanism involving interacting proteins that are secreted into germline cells by Wolbachia, and suggest new methods for insect control.
authors.affiliation: Department of Molecular Biophysics &Biochemistry, Yale University, 266 Whitney Avenue, New Haven, Connecticut 06520, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Beckmann
authors.affiliation: Department of Molecular Biophysics &Biochemistry, Yale University, 266 Whitney Avenue, New Haven, Connecticut 06520, USA.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Ronau
authors.affiliation: Department of Molecular Biophysics &Biochemistry, Yale University, 266 Whitney Avenue, New Haven, Connecticut 06520, USA.|Department of Molecular, Cellular, &Developmental Biology, Yale University, 266 Whitney Avenue, New Haven, Connecticut 06520, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Hochstrasser
mesh_terms: D000818:Animals; D003465:Culex / Q000382:microbiology* / Q000502:physiology*; D000072017:Deubiquitinating Enzymes / Q000378:metabolism*; D004330:Drosophila / Q000382:microbiology* / Q000502:physiology*; D008297:Male; D012098:Reproduction; D013094:Spermatozoa / Q000382:microbiology / Q000502:physiology; D020577:Wolbachia / Q000201:enzymology* / Q000254:growth & development / Q000378:metabolism
chemical_list: D000072017:Deubiquitinating Enzymes