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TitleA meiotic driver hijacks an epigenetic reader to disrupt mitosis in noncarrier offspring.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 121, Issue 45, Page e2408347121, Year 2024
Publish dateNov 5, 2024
AuthorsYu Hua / Jianxiu Zhang / Man-Yun Yang / Fan-Yi Zhang / Jing-Yi Ren / Xiao-Hui Lyu / Yan Ding / Fang Suo / Guang-Can Shao / Jun Li / Meng-Qiu Dong / Keqiong Ye / Li-Lin Du /
PubMed AbstractKiller meiotic drivers (KMDs) are selfish genetic elements that distort Mendelian inheritance by selectively killing meiotic products lacking the KMD element, thereby promoting their own propagation. ...Killer meiotic drivers (KMDs) are selfish genetic elements that distort Mendelian inheritance by selectively killing meiotic products lacking the KMD element, thereby promoting their own propagation. Although KMDs have been found in diverse eukaryotes, only a limited number of them have been characterized at the molecular level, and their killing mechanisms remain largely unknown. In this study, we identify that a gene previously deemed essential for cell survival in the fission yeast is a single-gene KMD. This gene, , kills nearly all progeny in a × cross. By analyzing polymorphisms of among natural strains, we identify a resistant haplotype, HT3. This haplotype lacks killing ability yet confers resistance to killing by the wild-type . Proximity labeling experiments reveal an interaction between Tdk1, the protein product of , and the epigenetic reader Bdf1. Interestingly, the nonkilling Tdk1-HT3 variant does not interact with Bdf1. Cryoelectron microscopy further elucidated the binding interface between Tdk1 and Bdf1, pinpointing mutations within Tdk1-HT3 that disrupt this interface. During sexual reproduction, Tdk1 forms stable Bdf1-binding nuclear foci in all spores after meiosis. These foci persist in germinated progeny and impede chromosome segregation during mitosis by generating aberrant chromosomal adhesions. This study identifies a KMD that masquerades as an essential gene and reveals the molecular mechanism by which this KMD hijacks cellular machinery to execute killing. Additionally, we unveil that losing the hijacking ability is an evolutionary path for this single-gene KMD to evolve into a nonkilling resistant haplotype.
External linksProc Natl Acad Sci U S A / PubMed:39485795
MethodsEM (single particle)
Resolution2.7 Å
Structure data

EMDB-61290, PDB-9ja5:
Cryo-EM structure of Tdk1-Bdf1 complex
Method: EM (single particle) / Resolution: 2.7 Å

Chemicals

ChemComp-HOH:
WATER

Source
  • schizosaccharomyces pombe 972h- (yeast)
  • streptococcus sp. group g (bacteria)
KeywordsCELL CYCLE / signaling protein / meiotic cell cycle

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