Journal Article

Prophage WO genes recapitulate and enhance Wolbachia-induced cytoplasmic incompatibility

Bordenstein, Sarah R., Perlmutter, Jessamyn I., Metcalf, Jason A., On, Jungmin, Funkhouser-Jones, Lisa J., Shropshire, J. Dylan, Beckmann, John F., LePage, Daniel P., Bordenstein, Seth R., Layton, Emily M.

2017

Overview

The discovery of two genes encoded by prophage WO from Wolbachia that functionally recapitulate and enhance cytoplasmic incompatibility in arthropods is the first inroad in solving the genetic basis of reproductive parasitism. Manipulation of insect survival by Wolbachia bacteria Bacteria from the genus Wolbachia infect many arthropods, including the mosquitoes that are vectors for many viruses that infect humans. Wolbachia infection causes 'cytoplasmic incompatibility', which means that crosses between infected males and uninfected females lead to embryonic death, increasing the proportion of infected females in the population. The molecular basis for this effect has been unknown. Here, Seth Bordenstein and colleagues use comparative and transgenic approaches to identify two genes encoded by the prophage WO from Wolbachia that recapitulate cytoplasmic incompatibility. The discovery of these cytoplasmic incompatibility factors could lead to the genetic manipulation of WO-induced reproductive alterations, and may feed into efforts to control the transmission of arthropod-borne viruses to humans. 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 1 and relevance to symbiont-induced speciation 2 , 3 , as well as control of arbovirus vectors 4 , 5 , 6 and agricultural pests 7 , 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 8 from Wolbachia strain w Mel 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 w Mel-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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/181/2474 / 631/181/735 / 631/208/325/1506 / 631/326/1321 / 631/326/432 / Animals / Animals, Genetically Modified / Bacteria / Biological Control Agents / Cell division / Cellular biology / Crosses, Genetic / Cytoplasm - genetics / Cytoplasm - pathology / Disease transmission / Drosophila melanogaster - cytology / Drosophila melanogaster - embryology / Drosophila melanogaster - microbiology / Drosophila melanogaster - physiology / Female / Females / Genes / Genes, Viral - genetics / Genomes / Host-Pathogen Interactions / Humanities and Social Sciences / letter / Male / multidisciplinary / Phylogenetics / Prophages - genetics / Proteins / Reproduction / Science / Sex Ratio / Speciation / Symbiosis / Vector-borne diseases / Wolbachia - classification / Wolbachia - genetics / Wolbachia - physiology / Wolbachia - virology