Crossover interference: Just ZYP it.
Crossover interference: Just ZYP it.
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交叉干扰：只需 ZYP 即可。
DOI：
10.1073/pnas.2103433118
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发表时间：
2021
影响因子：
11.1
通讯作者：
Crismani W
中科院分区：
文献类型：
--
作者：
Crismani W
一个多世纪以前，对果蝇的研究发现了适用于有性生殖生物的遗传基本机制。一个关键的观察结果是，在减数分裂（产生性细胞的细胞分裂）中，同源染色体进行大规模的遗传物质交换，称为交叉。第二个观察结果是，这些交叉不是随机分布的，一个交叉的存在降低了附近另一个交叉的可能性。这种现象被称为干扰，导致交叉间距比偶然预期的更均匀。直到今天，交叉干扰的机制在很大程度上仍未得到解释。在PNAS上，Capilla-Perez等人(2)和France等人(3)在我们对这一令人困惑的现象的理解上取得了飞跃。减数分裂交叉发生于前期I，在高度组织化的染色体结构中形成。首先，每条染色体的两个姐妹染色单体被拴在蛋白质轴上（图1）。其次，同源染色体轴被一个高度有序且进化上保守的结构“压缩”在一起：突触复合体。突触复合体的一个重复单位，类似于拉链的牙齿，是ZYP1蛋白，也被称为横向细丝。在PNAS上，Capilla-Perez等人(2)和France等人(3)利用拟南芥（Arabidopsis thaliana）的遗传工具阐明了横向细丝在交叉干扰中的作用。在拟南芥中，对横丝的遗传研究在很大程度上被排除在外，因为它是由ZYP1基因的反向复制编码的，该基因相隔2 kb，在前crispr /Cas9时代几乎不可能敲除。先前对多种生物的研究表明，交叉形成需要突触复合体及其横向细丝：在果蝇(4)、小鼠(5)、蠕虫(6)和酵母(7)中完全缺乏横向细丝，交叉形成严重减少。Capilla-Perez等人和France等人在拟南芥中产生了删除两个ZYP1拷贝的CRISPR/Cas9系，并报道该物种的交叉形成不需要横丝。重要的是，交叉仍然发生的事实为作者提供了一个机会来研究与交叉形成不直接相关的横向丝的其他作用，他们发现1)减数分裂过程可以在没有横向丝的情况下相对正常地进行：同源染色体排列但不能突触，正常的染色体轴重构被取消；2)突触复合体限制交叉并施加交叉干扰；3)正常情况下不同的雄性和雌性交叉率在没有横丝的情况下变得完全相同。
More than a century ago, research in Drosophila discovered fundamental mechanisms of inheritance that apply to sexually reproducing organisms (1). One key observation was that in meiosis, the cell division that generates sex cells, homologous chromosomes make large-scale reciprocal exchanges of genetic material called crossovers. A second observation was that these crossovers are not randomly distributed, with the presence of one crossover reducing the likelihood of another crossover nearby. This phenomenon, termed interference, results in crossover spacing that is more uniform than expected by chance. To this day, the mechanism of crossover interference remains largely unexplained. In PNAS, Capilla-Perez et al.(2) and France et al.(3) make a leap forward in our understanding of this puzzling phenomenon. Meiotic crossovers are formed during prophase I within a highly organized chromosome structure. First, the two sister chromatids of each chromosome are tethered to a proteinaceous axis (Fig. 1). Second, homologous chromosome axes are “zipped” together by a highly ordered and evolutionarily conserved structure: the synaptonemal complex. A repeating unit of the synaptonemal complex, which is analogous to the teeth of a zipper, is the ZYP1 protein, also called the transverse filament. In PNAS, Capilla-Perez et al.(2) and France et al.(3) leverage the genetic tools available for the plant Arabidopsis thaliana to elucidate the role of the transverse filament in crossover interference. Genetic studies of the transverse filament had been largely precluded in Arabidopsis because it is encoded by an inverted duplication of the ZYP1 gene separated by 2 kb, which was nearly impossible to knock out in the pre-CRISPR/Cas9 era. Previous studies in multiple organisms have shown that the synaptonemal complex, and its transverse filament, are required for crossover formation: In the complete absence of the transverse filament inDrosophila (4), mouse (5), worm (6), and yeast (7), crossover formation is severely reduced. Capilla-Perez et al. and France et al. generated CRISPR/Cas9 lines deleting both ZYP1 copies in Arabidopsis and reported that the transverse filament is not required for crossover formation in this species. Importantly, the fact that crossovers still occurred provided the authors an opportunity to investigate other roles of the transverse filament not directly related to crossover formation, and they found that 1) meiotic progression can proceed relatively normally without the transverse filament: Homologous chromosomes coalign but fail to synapse, and normal chromosome axis remodeling is abrogated; 2) the synaptonemal complex limits crossovers and imposes crossover interference; and 3) male and female crossover rates, which are normally different, become identical without the transverse filament.