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Male-killing symbiont damages host's dosage-compensated sex chromosome to induce embryonic apoptosis

View Article: PubMed Central - PubMed

ABSTRACT

Some symbiotic bacteria are capable of interfering with host reproduction in selfish ways. How such bacteria can manipulate host's sex-related mechanisms is of fundamental interest encompassing cell, developmental and evolutionary biology. Here, we uncover the molecular and cellular mechanisms underlying Spiroplasma-induced embryonic male lethality in Drosophila melanogaster. Transcriptomic analysis reveals that many genes related to DNA damage and apoptosis are up-regulated specifically in infected male embryos. Detailed genetic and cytological analyses demonstrate that male-killing Spiroplasma causes DNA damage on the male X chromosome interacting with the male-specific lethal (MSL) complex. The damaged male X chromosome exhibits a chromatin bridge during mitosis, and bridge breakage triggers sex-specific abnormal apoptosis via p53-dependent pathways. Notably, the MSL complex is not only necessary but also sufficient for this cytotoxic process. These results highlight symbiont's sophisticated strategy to target host's sex chromosome and recruit host's molecular cascades toward massive apoptosis in a sex-specific manner.

No MeSH data available.


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Model for the mechanism of Spiroplasma-induced male-killing in Drosophila.(a) The time line of male-killing phenotypes during embryogenesis. Mitotic cycles are shown below the line. First 13 cleavage cycles are rapid and synchronous, consisting of only S and M phases. After cellularization at stage 5, cells obtain G2 phase and undergo three rounds of mitosis with specific pattern and timing (cycle 14–16), followed by G1 arrest. (b) The cytological model of Spiroplasma-induced male-killing. See the text for details.
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f7: Model for the mechanism of Spiroplasma-induced male-killing in Drosophila.(a) The time line of male-killing phenotypes during embryogenesis. Mitotic cycles are shown below the line. First 13 cleavage cycles are rapid and synchronous, consisting of only S and M phases. After cellularization at stage 5, cells obtain G2 phase and undergo three rounds of mitosis with specific pattern and timing (cycle 14–16), followed by G1 arrest. (b) The cytological model of Spiroplasma-induced male-killing. See the text for details.

Mentions: In this study, we uncovered a number of previously unrecognized molecular and cellular aspects underlying Spiroplasma-induced male-killing during Drosophila's embryogenesis, which include: (i) a large number of genes related to DNA damage and apoptosis are up-regulated specifically in Spiroplasma-infected male embryos (Fig. 1; Supplementary Fig. 1; Supplementary Data 1); (ii) Spiroplasma causes DNA damage on the male X chromosome interacting with the functional MSL complex (Fig. 3 and Supplementary Fig. 2); (iii) the damaged male X chromosome exhibits chromosomal bridge and breakage during cell division (Fig. 4 and Supplementary Fig. 3); (iv) the functional MSL complex is not only necessary but also sufficient for triggering Spiroplasma-induced DNA damage, chromatin bridge and apoptosis (Fig. 5 and Supplementary Fig. 4); (v) bridge breakage in the male X chromosome is responsible for abnormal apoptosis via p53-dependent pathways (Fig. 2); and (vi) the mitosis-associated chromatin bridge-breakage is preceded by the induction of chromosome-specific DNA damage (Fig. 6). On the basis of these results, we propose a hypothetical model as to what molecular and cellular mechanisms are operating in the developmental events of Spiroplasma-infected male embryos, which finally result in massive apoptosis and associated developmental abnormalities leading to male-specific embryonic lethality (Fig. 7). In conclusion, Spiroplasma targets the dosage-compensated male X chromosome with the clue of the functional MSL complex and somehow introduces DNA damage on it, thereby causing male-specific chromosomal segregation defects and recruiting host's p53-dependent pathways to induce apoptosis.


Male-killing symbiont damages host's dosage-compensated sex chromosome to induce embryonic apoptosis
Model for the mechanism of Spiroplasma-induced male-killing in Drosophila.(a) The time line of male-killing phenotypes during embryogenesis. Mitotic cycles are shown below the line. First 13 cleavage cycles are rapid and synchronous, consisting of only S and M phases. After cellularization at stage 5, cells obtain G2 phase and undergo three rounds of mitosis with specific pattern and timing (cycle 14–16), followed by G1 arrest. (b) The cytological model of Spiroplasma-induced male-killing. See the text for details.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5036004&req=5

f7: Model for the mechanism of Spiroplasma-induced male-killing in Drosophila.(a) The time line of male-killing phenotypes during embryogenesis. Mitotic cycles are shown below the line. First 13 cleavage cycles are rapid and synchronous, consisting of only S and M phases. After cellularization at stage 5, cells obtain G2 phase and undergo three rounds of mitosis with specific pattern and timing (cycle 14–16), followed by G1 arrest. (b) The cytological model of Spiroplasma-induced male-killing. See the text for details.
Mentions: In this study, we uncovered a number of previously unrecognized molecular and cellular aspects underlying Spiroplasma-induced male-killing during Drosophila's embryogenesis, which include: (i) a large number of genes related to DNA damage and apoptosis are up-regulated specifically in Spiroplasma-infected male embryos (Fig. 1; Supplementary Fig. 1; Supplementary Data 1); (ii) Spiroplasma causes DNA damage on the male X chromosome interacting with the functional MSL complex (Fig. 3 and Supplementary Fig. 2); (iii) the damaged male X chromosome exhibits chromosomal bridge and breakage during cell division (Fig. 4 and Supplementary Fig. 3); (iv) the functional MSL complex is not only necessary but also sufficient for triggering Spiroplasma-induced DNA damage, chromatin bridge and apoptosis (Fig. 5 and Supplementary Fig. 4); (v) bridge breakage in the male X chromosome is responsible for abnormal apoptosis via p53-dependent pathways (Fig. 2); and (vi) the mitosis-associated chromatin bridge-breakage is preceded by the induction of chromosome-specific DNA damage (Fig. 6). On the basis of these results, we propose a hypothetical model as to what molecular and cellular mechanisms are operating in the developmental events of Spiroplasma-infected male embryos, which finally result in massive apoptosis and associated developmental abnormalities leading to male-specific embryonic lethality (Fig. 7). In conclusion, Spiroplasma targets the dosage-compensated male X chromosome with the clue of the functional MSL complex and somehow introduces DNA damage on it, thereby causing male-specific chromosomal segregation defects and recruiting host's p53-dependent pathways to induce apoptosis.

View Article: PubMed Central - PubMed

ABSTRACT

Some symbiotic bacteria are capable of interfering with host reproduction in selfish ways. How such bacteria can manipulate host's sex-related mechanisms is of fundamental interest encompassing cell, developmental and evolutionary biology. Here, we uncover the molecular and cellular mechanisms underlying Spiroplasma-induced embryonic male lethality in Drosophila melanogaster. Transcriptomic analysis reveals that many genes related to DNA damage and apoptosis are up-regulated specifically in infected male embryos. Detailed genetic and cytological analyses demonstrate that male-killing Spiroplasma causes DNA damage on the male X chromosome interacting with the male-specific lethal (MSL) complex. The damaged male X chromosome exhibits a chromatin bridge during mitosis, and bridge breakage triggers sex-specific abnormal apoptosis via p53-dependent pathways. Notably, the MSL complex is not only necessary but also sufficient for this cytotoxic process. These results highlight symbiont's sophisticated strategy to target host's sex chromosome and recruit host's molecular cascades toward massive apoptosis in a sex-specific manner.

No MeSH data available.


Related in: MedlinePlus