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

Abstract

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.

Author Summary

Pathogens are known to manipulate the physiology, behavior, and reproduction of their hosts for their own benefit. The endosymbiotic bacterium Wolbachia is known to manipulate the sex of its host's progeny. Male-killing is one of the phenotypes that Wolbachia induces, but the mechanism of how Wolbachia induces sex-specific death is unknown. Here we found a marked down-regulation of Masc, a lepidopteran-specific zinc finger protein gene, in embryos that are produced by Wolbachia-infected Ostrinia moths. We also observed that dosage compensation fails in Wolbachia-infected Ostrinia embryos. The findings of this study and our previous study using a lepidopteran model insect Bombyx mori indicate that Wolbachia has evolved to hijack the Masc-dependent, lepidopteran insect-specific sex determination system by capturing an unknown factor during Wolbachia-host coevolution.