John Innes Centre, Norwich Research Park, Norwich, UK.
Department of Plant Sciences, University of Cambridge, Cambridge, UK.
Nat Commun. 2021 Aug 3;12(1):4674. doi: 10.1038/s41467-021-24827-w.
In most organisms, the number and distribution of crossovers that occur during meiosis are tightly controlled. All chromosomes must receive at least one 'obligatory crossover' and crossovers are prevented from occurring near one another by 'crossover interference'. However, the mechanistic basis of this phenomenon of crossover interference has remained mostly mysterious. Using quantitative super-resolution cytogenetics and mathematical modelling, we investigate crossover positioning in the Arabidopsis thaliana wild-type, an over-expressor of the conserved E3 ligase HEI10, and a hei10 heterozygous line. We show that crossover positions can be explained by a predictive, diffusion-mediated coarsening model, in which large, approximately evenly-spaced HEI10 foci grow at the expense of smaller, closely-spaced clusters. We propose this coarsening process explains many aspects of Arabidopsis crossover positioning, including crossover interference. Consistent with this model, we also demonstrate that crossover positioning can be predictably modified in vivo simply by altering HEI10 dosage, with higher and lower dosage leading to weaker and stronger crossover interference, respectively. As HEI10 is a conserved member of the RING finger protein family that functions in the interference-sensitive pathway for crossover formation, we anticipate that similar mechanisms may regulate crossover positioning in diverse eukaryotes.
在大多数生物体中，减数分裂过程中发生的交叉点的数量和分布受到严格控制。所有染色体都必须至少收到一个“必需交叉点”，并且通过“交叉干扰”防止交叉点彼此靠近。然而，这种交叉干扰现象的机制基础在很大程度上仍然是神秘的。使用定量超分辨率细胞遗传学和数学建模，我们研究了拟南芥野生型、保守 E3 连接酶 HEI10 的过表达体和 hei10 杂合系中的交叉点定位。我们表明，交叉点的位置可以通过预测性、扩散介导的粗化模型来解释，在该模型中，较大的、大致均匀间隔的 HEI10 焦点会消耗较小的、紧密间隔的簇来生长。我们提出，这种粗化过程解释了拟南芥交叉点定位的许多方面，包括交叉干扰。与该模型一致，我们还证明，通过简单地改变 HEI10 的剂量，体内的交叉点定位可以可预测地进行修改，较高和较低的剂量分别导致较弱和较强的交叉干扰。由于 HEI10 是 RING 指蛋白家族的保守成员，该家族在交叉形成的干扰敏感途径中发挥作用，我们预计类似的机制可能会调节不同真核生物中的交叉点定位。
