According to the Dobzhansky-Muller model, hybrid sterility is a consequence of the independent evolution of related taxa resulting in incompatible genomic interactions of their hybrids. The model implies that the incompatibilities evolve randomly, unless a particular gene or nongenic sequence diverges much faster than the rest of the genome. Here we propose that asynapsis of heterospecific chromosomes in meiotic prophase provides a recurrently evolving trigger for the meiotic arrest of interspecific F1 hybrids. We observed extensive asynapsis of chromosomes and disturbance of the sex body in >95% of pachynemas of Mus m. musculus × Mus m. domesticus sterile F1 males. Asynapsis was not preceded by a failure of double-strand break induction, and the rate of meiotic crossing over was not affected in synapsed chromosomes. DNA double-strand break repair was delayed or failed in unsynapsed autosomes, and misexpression of chromosome X and chromosome Y genes was detected in single pachynemas and by genome-wide expression profiling. Oocytes of F1 hybrid females showed the same kind of synaptic problems but with the incidence reduced to half. Most of the oocytes with pachytene asynapsis were eliminated before birth. We propose the heterospecific pairing of homologous chromosomes as a preexisting condition of asynapsis in interspecific hybrids. The asynapsis may represent a universal mechanistic basis of F1 hybrid sterility manifested by pachytene arrest. It is tempting to speculate that a fast-evolving subset of the noncoding genomic sequence important for chromosome pairing and synapsis may be the culprit.

• MeSH
• apoptóza genetika   MeSH
• biologická evoluce MeSH
• biologické modely MeSH
• druhová specificita MeSH
• dvouřetězcové zlomy DNA MeSH
• inbrední kmeny myší klasifikace   genetika   fyziologie   MeSH
• infertilita genetika   patologie   patofyziologie   MeSH
• křížení genetické MeSH
• meióza genetika   MeSH
• myši inbrední BALB C MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• oocyty patologie   MeSH
• párování chromozomů genetika   MeSH
• rekombinace genetická MeSH
• spermatocyty patologie   MeSH
• spermatogeneze genetika   MeSH
• těhotenství MeSH
• transkriptom MeSH
• vznik druhů (genetika) MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Chromosome segregation errors are highly frequent in mammalian female meiosis, and their incidence gradually increases with maternal age. The fate of aneuploid eggs is obviously dependent on the stringency of mechanisms for detecting unattached or repairing incorrectly attached kinetochores. In case of their failure, the newly formed embryo will inherit the impaired set of chromosomes, which will have severe consequences for its further development. Whether spindle assembly checkpoint (SAC) in oocytes is capable of arresting cell cycle progression in response to unaligned kinetochores was discussed for a long time. It is known that abolishing SAC increases frequency of chromosome segregation errors and causes precocious entry into anaphase; SAC, therefore, seems to be essential for normal chromosome segregation in meiosis I. However, it was also reported that for anaphase-promoting complex (APC) activation, which is a prerequisite for entering anaphase; alignment of only a critical mass of kinetochores on equatorial plane is sufficient. This indicates that the function of SAC and of cooperating chromosome attachment correction mechanisms in oocytes is different from somatic cells. To analyze this phenomenon, we used live cell confocal microscopy to monitor chromosome movements, spindle formation, APC activation and polar body extrusion (PBE) simultaneously in individual oocytes at various time points during first meiotic division. Our results, using oocytes from aged animals and interspecific crosses, demonstrate that multiple unaligned kinetochores and severe congression defects are tolerated at the metaphase to anaphase transition, although such cells retain sensitivity to nocodazole. This indicates that checkpoint mechanisms, operating in oocytes at this point, are essential for accurate timing of APC activation in meiosis I, but they are insufficient in detection or correction of unaligned chromosomes, preparing thus conditions for propagation of the aneuploidy to the embryo.

• MeSH
• anafáze MeSH
• anafázi podporující komplex MeSH
• aneuploidie MeSH
• časosběrné zobrazování metody   MeSH
• histony genetika   metabolismus   MeSH
• kinetochory metabolismus   MeSH
• komplexy ubikvitinligas genetika   metabolismus   MeSH
• konfokální mikroskopie metody   MeSH
• kontrolní body M fáze buněčného cyklu MeSH
• metafáze MeSH
• mikroinjekce MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• oocyty cytologie   metabolismus   MeSH
• párování chromozomů * MeSH
• proteolýza MeSH
• savčí chromozomy genetika   metabolismus   MeSH
• savci MeSH
• segregace chromozomů * MeSH
• sekurin MeSH
• transportní proteiny genetika   metabolismus   MeSH
• tubulin genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• anafázi podporující komplex MeSH
• histony MeSH
• komplexy ubikvitinligas MeSH
• sekurin MeSH
• transportní proteiny MeSH
• tubulin MeSH