title: Prophage WO genes recapitulate and enhance Wolbachia-induced cytoplasmic incompatibility.
abstract: The genus Wolbachia is an archetype of maternally inherited intracellular bacteria that infect the germline of numerous invertebrate species worldwide. They can selfishly alter arthropod sex ratios and reproductive strategies to increase the proportion of the infected matriline in the population. The most common reproductive manipulation is cytoplasmic incompatibility, which results in embryonic lethality in crosses between infected males and uninfected females. Females infected with the same Wolbachia strain rescue this lethality. Despite more than 40 years of research and relevance to symbiont-induced speciation, as well as control of arbovirus vectors and agricultural pests, the bacterial genes underlying cytoplasmic incompatibility remain unknown. Here we use comparative and transgenic approaches to demonstrate that two differentially transcribed, co-diverging genes in the eukaryotic association module of prophage WO from Wolbachia strain wMel recapitulate and enhance cytoplasmic incompatibility. Dual expression in transgenic, uninfected males of Drosophila melanogaster crossed to uninfected females causes embryonic lethality. Each gene additively augments embryonic lethality in crosses between infected males and uninfected females. Lethality associates with embryonic defects that parallel those of wild-type cytoplasmic incompatibility and is notably rescued by wMel-infected embryos in all cases. The discovery of cytoplasmic incompatibility factor genes cifA and cifB pioneers genetic studies of prophage WO-induced reproductive manipulations and informs the continuing use of Wolbachia to control dengue and Zika virus transmission to humans.
authors.affiliation: Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37235, USA.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: LePage
authors.affiliation: Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37235, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Metcalf
authors.affiliation: Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37235, USA.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Bordenstein
authors.affiliation: Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37235, USA.
authors.forename: Jungmin
authors.initials: J
authors.lastname: On
authors.affiliation: Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37235, USA.
authors.forename: Jessamyn I
authors.initials: JI
authors.lastname: Perlmutter
authors.affiliation: Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37235, USA.
authors.forename: J Dylan
authors.initials: JD
authors.lastname: Shropshire
authors.affiliation: Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37235, USA.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Layton
authors.affiliation: Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37235, USA.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Funkhouser-Jones
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Beckmann
authors.affiliation: Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37235, USA.|Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, Tennessee 37235, USA.
authors.forename: Seth R
authors.initials: SR
authors.lastname: Bordenstein
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D061046:Biological Control Agents; D003433:Crosses, Genetic; D003593:Cytoplasm / Q000235:genetics* / Q000473:pathology; D004331:Drosophila melanogaster / Q000166:cytology* / Q000196:embryology / Q000382:microbiology* / Q000502:physiology; D005260:Female; D005814:Genes, Viral / Q000235:genetics*; D054884:Host-Pathogen Interactions; D008297:Male; D039002:Prophages / Q000235:genetics*; D012098:Reproduction; D012744:Sex Ratio; D013559:Symbiosis; D020577:Wolbachia / Q000145:classification / Q000235:genetics* / Q000502:physiology / Q000821:virology
chemical_list: D061046:Biological Control Agents