The Endosymbiotic Bacterium Wolbachia Selectively Kills Male Hosts by Targeting the Masculinizing Gene

• DOI: 10.1371/journal.ppat.1005048
• Publication Date: 2015-07-14T18:05:02Z
• Authors: Takahiro Fukui; Munetaka Kawamoto; Keisuke Shoji; Takashi Kiuchi; Sumio Sugano; Toru Shimada; Yutaka Suzuki; Susumu Katsuma
• Keywords: Male; 0301 basic medicine; QH301-705.5; Reverse Transcriptase Polymerase Chain Reaction; Molecular Sequence Data; Zinc Fingers; RC581-607; Moths; Transfection; 03 medical and health sciences; Animals; Female; Immunologic diseases. Allergy; Biology (General); Phylogeny; Wolbachia; Research Article

Pathogens are known to manipulate the reproduction and development of their hosts for their own benefit. Wolbachia is an endosymbiotic bacterium that infects a wide range of insect species. Wolbachia is known as an example of a parasite that manipulates the sex of its host's progeny. Infection of Ostrinia moths by Wolbachia causes the production of all-female progeny, however, the mechanism of how Wolbachia accomplishes this male-specific killing is unknown. Here we show for the first time that Wolbachia targets the host masculinizing gene of Ostrinia to accomplish male-killing. We found that Wolbachia-infected O. furnacalis embryos do not express the male-specific splice variant of doublesex, a gene which acts at the downstream end of the sex differentiation cascade, throughout embryonic development. Transcriptome analysis revealed that Wolbachia infection markedly reduces the mRNA level of Masc, a gene that encodes a protein required for both masculinization and dosage compensation in the silkworm Bombyx mori. Detailed bioinformatic analysis also elucidated that dosage compensation of Z-linked genes fails in Wolbachia-infected O. furnacalis embryos, a phenomenon that is extremely similar to that observed in Masc mRNA-depleted male embryos of B. mori. Finally, injection of in vitro transcribed Masc cRNA into Wolbachia-infected embryos rescued male progeny. Our results show that Wolbachia-induced male-killing is caused by a failure of dosage compensation via repression of the host masculinizing gene. Our study also shows a novel strategy by which a pathogen hijacks the host sex determination cascade.