Male-Killing Spiroplasma Alters Behavior of the Dosage Compensation Complex during Drosophila melanogaster Embryogenesis

• Published in: Current biology 2016-05, Vol.26 (10), p.1339-1345
• Main Authors: Cheng, Becky, Kuppanda, Nitin, Aldrich, John C., Akbari, Omar S., Ferree, Patrick M.
• Format: Article
• Language: English
• Subjects: Animals; Dosage Compensation, Genetic; Drosophila melanogaster - embryology; Drosophila melanogaster - genetics; Drosophila melanogaster - microbiology; Embryonic Development; Male; Spiroplasma - physiology
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2016.03.050

Numerous arthropods harbor maternally transmitted bacteria that induce the preferential death of males [1–7]. This sex-specific lethality benefits the bacteria because males are “dead ends” regarding bacterial transmission, and their absence may result in additional resources for their viable female siblings who can thereby more successfully transmit the bacteria [5]. Although these symbionts disrupt a range of developmental processes [8–10], the underlying cellular mechanisms are largely unknown. It was previously shown that mutations in genes of the dosage compensation pathway of Drosophila melanogaster suppressed male killing caused by the bacterium, Spiroplasma [10]. This result suggested that dosage compensation is a target of Spiroplasma. However, it remains unclear how this pathway is affected, and whether the underlying interactions require the male-specific cellular environment. Here, we investigated the cellular basis of male embryonic lethality in D. melanogaster induced by Spiroplasma. We found that the dosage compensation complex (DCC), which acetylates X chromatin in males [11], becomes mis-localized to ectopic regions of the nucleus immediately prior to the killing phase. This effect was accompanied by inappropriate histone acetylation and genome-wide mis-regulation of gene expression. Artificially induced formation of the DCC in infected females, through transgenic expression of the DCC-specific gene msl-2, resulted in mis-localization of this complex to non-X regions and early Spiroplasma-induced death, mirroring the killing effects in males. These findings strongly suggest that Spiroplasma initiates male killing by targeting the dosage compensation machinery directly and independently of other cellular features characteristic of the male sex. •The DCC becomes mis-localized in Spiroplasma-infected male fruit fly embryos•Infected males exhibit ectopic H4K16 acetylation and genome-wide gene mis-expression•Infection leads to death of females artificially expressing the DCC Cheng et al. show that infection of the fruit fly with a male-killing Spiroplasma strain causes mis-localization of the dosage compensation complex (DCC) and abnormal gene expression in young male embryos, and death of females artificially expressing low levels of this complex. The bacterium may therefore target the DCC directly to kill males.