Centromere strength provides the cell biological basis for meiotic drive and karyotype evolution in mice.

Centromere strength provides the cell biological basis for meiotic drive and karyotype evolution in mice.
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DOI:
10.1016/j.cub.2014.08.017
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发表时间:
2014-10-06
期刊:
Current biology : CB
影响因子:
--
通讯作者:
Lampson MA
Lampson MA
中科院分区:
其他
文献类型:
--
作者:
Chmátal L;Gabriel SI;Mitsainas GP;Martínez-Vargas J;Ventura J;Searle JB;Schultz RM;Lampson MA

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哺乳动物的核型(染色体的数量和结构)可以在很短的进化时间内发生巨大变化。在102-105年中,有大量的核型转换的例子,从大多数端着丝粒(着丝粒末端)到大多数中着丝粒(着丝粒内部)。这些变化通常反映了罗伯逊(Rb)融合的快速固定,这是一种常见的染色体重排,将两个端部着丝粒染色体在其着丝粒处连接以产生一个中部着丝粒。Rb融合体的固定可以用减数分裂驱动来解释:在雌性减数分裂期间违反孟德尔第一定律的偏向性染色体分离。然而,没有机制解释为什么融合会优先分离到一些人群中的卵子,导致固定和核型变化,而其他人群优先消除融合并保持端着丝粒核型。在这里,我们表明,使用实验室模型和野生小鼠,在着丝粒强度的差异预测驱动器的方向。较强的着丝粒,表现为增加动粒蛋白水平和改变与纺锤体微管的相互作用,优先保留在鸡蛋。我们发现,在实验室小鼠品系的融合优先分离的极体时,融合着丝粒比端着丝粒弱。相反,融合着丝粒相对于自然家鼠种群中的端着丝粒更强,这些家鼠种群通过积累中着丝粒融合而改变了核型。我们的研究结果表明,着丝粒强度的自然变化解释了驱动力的方向如何在种群之间切换。它们也为着丝粒驱动和核型进化提供了细胞生物学基础。
Mammalian karyotypes (number and structure of chromosomes) can vary dramatically over short evolutionary time frames. There are examples of massive karyotype conversion, from mostly telocentric (centromere terminal) to mostly metacentric (centromere internal), in 102–105 years. These changes typically reflect rapid fixation of Robertsonian (Rb) fusions, a common chromosomal rearrangement that joins two telocentric chromosomes at their centromeres to create one metacentric. Fixation of Rb fusions can be explained by meiotic drive: biased chromosome segregation during female meiosis in violation of Mendel’s First Law. However, there is no mechanistic explanation of why fusions would preferentially segregate to the egg in some populations, leading to fixation and karyotype change, while other populations preferentially eliminate the fusions and maintain a telocentric karyotype. Here we show, using both laboratory models and wild mice, that differences in centromere strength predict the direction of drive. Stronger centromeres, manifested by increased kinetochore protein levels and altered interactions with spindle microtubules, are preferentially retained in the egg. We find that fusions preferentially segregate to the polar body in laboratory mouse strains when the fusion centromeres are weaker than those of telocentrics. Conversely, fusion centromeres are stronger relative to telocentrics in natural house mouse populations that have changed karyotype by accumulating metacentric fusions. Our findings suggest that natural variation in centromere strength explains how the direction of drive can switch between populations. They also provide a cell biological basis of centromere drive and karyotype evolution.
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