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

Abstract

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.

Crossover patterning through kinase-regulated condensation and coarsening of recombination nodules

“…This evidence that proteins can move along the interface between paired chromosomes suggested a potential mechanism for communication between and patterning of recombination nodules (Zhang et al, 2018). A recent study proposed a mechanism based on diffusion and coarsening of an essential RN component along chromosomes (Morgan et al, 2021), similar to the model presented here.…”

“…Competition is reduced as the distance between nodules increases due to the time required for diffusion and the presence of intervening nodules. These aspects of the model are similar to the diffusion-mediated coarsening of Hei10 that was recently proposed for Arabidopsis (Morgan et al, 2021). These models predict that RNs at the end of the SC are less likely to survive (Figure 7D) and that surviving LRNs are spaced farther apart than randomly selected ERNs (Figure 7E), i.e., that they show interference.…”

Quantitative modelling of fine-scale variations in the Arabidopsis thaliana crossover landscape

“…Similarly, we have not explicitly included CO interference or the obligatory CO, we have just incorporated a proxy of their effects via chromosome-specific rescalings. Such a choice is in line with the expectation that CO interference and the obligatory CO shape recombination landscapes on large scales (Lloyd & Jenczewski, 2019;Morgan et al, 2021), leaving open the determinants at fine scales. Lastly, but perhaps very importantly, we take no account of the well-known fact that meiotic chromosomes are organised in loops tethered to an axis.…”

Caught in the Act: Live-Cell Imaging of Plant Meiosis

“…As recently shown by immuno-cytochemistry, the E3 ligase HEI10, which is a crucial determinant of type I COs and CO interference, is present along the chromosome axis in early pachytene. It then accumulates in growing foci, which are evenly distributed at the expense of smaller, closely spaced peaks in mid and late pachytene (Morgan et al, 2021). It will be now very interesting to follow these foci in real time and correlate their dynamics with other type I CO components by live-cell imaging.…”