The Endosymbiotic Bacterium <i>Wolbachia</i> Selectively Kills Male Hosts by Targeting the Masculinizing Gene

<div><p>Pathogens are known to manipulate the reproduction and development of their hosts for their own benefit. <i>Wolbachia</i> is an endosymbiotic bacterium that infects a wide range of insect species. <i>Wolbachia</i> is known as an example of a parasite that manipulates the sex of its host's progeny. Infection of <i>Ostrinia</i> moths by <i>Wolbachia</i> causes the production of all-female progeny, however, the mechanism of how <i>Wolbachia</i> accomplishes this male-specific killing is unknown. Here we show for the first time that <i>Wolbachia</i> targets the host masculinizing gene of <i>Ostrinia</i> to accomplish male-killing. We found that <i>Wolbachia</i>-infected <i>O</i>. <i>furnacalis</i> embryos do not express the male-specific splice variant of <i>doublesex</i>, 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 <i>Masc</i>, a gene that encodes a protein required for both masculinization and dosage compensation in the silkworm <i>Bombyx mori</i>. Detailed bioinformatic analysis also elucidated that dosage compensation of Z-linked genes fails in <i>Wolbachia</i>-infected <i>O</i>. <i>furnacalis</i> embryos, a phenomenon that is extremely similar to that observed in <i>Masc</i> mRNA-depleted male embryos of <i>B</i>. <i>mori</i>. Finally, injection of <i>in vitro</i> transcribed <i>Masc</i> cRNA into <i>Wolbachia</i>-infected embryos rescued male progeny. Our results show that <i>Wolbachia</i>-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.</p></div>