Coarsening dynamics can explain meiotic crossover patterning in both the presence and absence of the synaptonemal complex

Abstract

The shuffling of genetic material facilitated by meiotic crossovers is a critical driver of genetic variation. Therefore, the number and positions of crossover events must be carefully controlled. In Arabidopsis, an obligate crossover and repression of nearby crossovers on each chromosome pair are abolished in mutants that lack the synaptonemal complex (SC), a conserved protein scaffold. We use mathematical modelling and quantitative super-resolution microscopy to explore and mechanistically explain meiotic crossover pattering in Arabidopsis lines with full, incomplete or abolished synapsis. For zyp1 mutants, which lack an SC, we develop a coarsening model in which crossover precursors globally compete for a limited pool of the pro-crossover factor HEI10, with dynamic HEI10 exchange mediated through the nucleoplasm. We demonstrate that this model is capable of quantitatively reproducing and predicting zyp1 experimental crossover patterning and HEI10 foci intensity data. Additionally, we find that a model combining both SC- and nucleoplasm-mediated coarsening can explain crossover patterning in wild-type Arabidopsis and in pch2 mutants, which display partial synapsis. Together, our results reveal that regulation of crossover patterning in wild-type Arabidopsis and SC defective mutants likely act through the same underlying coarsening mechanism, differing only in the spatial compartments through which the pro-crossover factor diffuses.

Uncharted territories: Solving the mysteries of male meiosis in flies

“…This change in the number and structure of AHC foci is remarkably similar to protein diffusion and "coarsening" observed recently for pro-CO factors in plants and nematodes [44][45][46][47][48]. Accurate homolog segregation in meiosis I in these and many other species is ensured by the formation of COs that link homologs together until anaphase I. CO formation is tightly regulated: there needs to be at least 1 CO per chromosome pair, but not more than a few COs, and the COs that do form need to be spatially separated along the chromosome axis (CO assurance and CO interference, respectively; reviewed in [49,50]).…”

Meiotic recombination dynamics in plants with repeat-based holocentromeres shed light on the primary drivers of crossover patterning

“…This late involvement in synapsis means a potential delay in DSB formation and HEI10 loading, which is consistent with the lower recombination frequency observed at the 35S rDNA-harbouring ends of chromosomes 1 and 2. Here, we show that the CO distal bias is present even in the absence of compartmentalised chromosomal features, strongly suggesting that telomere-led pairing and synapsis initiation alone can impose CO bias 54,[57][58][59] . However, we cannot exclude that other factor, like a different density of DSBs along chromosomes might contribute to the U-shape distribution of COs 60 .…”

The regulation of meiotic crossover distribution: a coarse solution to a century-old mystery?

“…(v) The HEI10 dosage and SC length have a combined effect; increasing the HEI10 dosage increases CO proportionally to the SC length [ 70 ]. (vi) CO interference among class I COs is abolished in the absence of the transverse filament of the SC in Arabidopsis [ 34 , 72 , 73 ] and rice [ 74 , 75 ]. This is interpreted in the context of the coarsening model as follows: in the absence of the SC, diffusion of HEI10 molecules occurs within the whole nucleoplasm and these can form foci on recombination intermediates to promote CO formation throughout the nucleus.…”

“…This is interpreted in the context of the coarsening model as follows: in the absence of the SC, diffusion of HEI10 molecules occurs within the whole nucleoplasm and these can form foci on recombination intermediates to promote CO formation throughout the nucleus. Diffusion being no longer constrained by the SC, the process is now blind to chromosomes, abolishing CO interference, the obligate CO, and the male–female CO difference that is imposed by different SC lengths [ 34 , 70 , 73 ]. (vii) Disturbing the integrity of the SC, through diminishing the amount of SC protein or removal of SC proteins, allows for more crossovers to form per chromosome [ 49 , 76 , 77 ].…”