Diffusion-mediated HEI10 coarsening can explain meiotic crossover positioning in Arabidopsis

背景回顾：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’. 

提出问题：However, the mechanistic basis of this phenomenon of crossover interference has remained mostly mysterious.

主要研究：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. 

结果1-粗粒化模型：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. 

结果2-模型解释交换干扰：We propose this coarsening process explains many aspects of Arabidopsis crossover positioning, including crossover interference. 

结果3-调控交换干扰强度：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. 

结论：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.

 摘 要 

在大多数生物中，减数分裂时期发生交换（crossover）的次数和分布是受到严格的控制的。所有的染色体必须至少发生一次所谓的“强制性交换”，并且通过“交换干扰”的机制避免两次交换发生在彼此的附近位置。但是，“交换干扰”现象的机制还不清楚。本文中，作者利用定量超高分辨率的细胞遗传学和数学建模，研究了拟南芥野生型、保守的E3连接酶HEI10过表达和hei10杂合突变株系的交换定位情况。作者发现，交换位置可以用一个预测性的、扩散介导的粗粒化模型来解释，在该模型中，通过牺牲较小的、紧密分布的HEI10簇为代价，从而形成大的、近似均匀分布的HEI10中心。作者发现该粗粒化模型能够解释拟南芥中交换定位的多个方面，包括交换干扰。与此模型一致，作者还发现交换定位能够通过改变HEI10的剂量来体内调控交换定位，高（低）的HEI10剂量会导致更弱（强）的交换干扰。因为HEI10是RING finger蛋白家族的一个较为保守的蛋白，作用于交换形成时的干扰敏感通路，因此作者推测在其他的真核生物中可能存在类似的机制调控交换定位。