Cell Biology and Biophysics, European Molecular Biology Laboratory, Heidelberg, Germany.
Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Nat Cell Biol. 2024 Sep;26(9):1496-1503. doi: 10.1038/s41556-024-01485-w. Epub 2024 Aug 8.
The eukaryotic cell division machinery must rapidly and reproducibly duplicate and partition the cell's chromosomes in a carefully coordinated process. However, chromosome numbers vary dramatically between genomes, even on short evolutionary timescales. We sought to understand how the mitotic machinery senses and responds to karyotypic changes by using a series of budding yeast strains in which the native chromosomes have been successively fused. Using a combination of cell biological profiling, genetic engineering and experimental evolution, we show that chromosome fusions are well tolerated up until a critical point. Cells with fewer than five centromeres lack the necessary number of kinetochore-microtubule attachments needed to counter outward forces in the metaphase spindle, triggering the spindle assembly checkpoint and prolonging metaphase. Our findings demonstrate that spindle architecture is a constraining factor for karyotype evolution.
真核细胞分裂机制必须快速且可重复地复制和分割细胞的染色体，这个过程需要精心协调。然而，即使在短时间的进化尺度上，染色体数量在不同基因组之间也存在显著差异。我们通过一系列连续融合天然染色体的酿酒酵母菌株，旨在了解有丝分裂机制如何感知和响应核型变化。我们采用细胞生物学分析、遗传工程和实验进化相结合的方法，表明染色体融合在一个关键临界点之前是可以很好地耐受的。具有少于五个着丝粒的细胞缺乏足够数量的动粒微管附着，以抵消中期纺锤体的向外力，从而触发纺锤体组装检查点并延长中期。我们的研究结果表明，纺锤体结构是核型进化的制约因素。
