ASY1 acts as a dosage-dependent antagonist of telomere-led recombination and mediates crossover interference in Arabidopsis

Andrew J Tock,Ian R Henderson,Christophe Lambing,Pallas C Kuo,Stephanie D Topp

doi:10.1073/pnas.1921055117

Andrew J Tock, Ian R Henderson + Show 3 more

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https://doi.org/10.1073/pnas.1921055117

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Abstract

During meiosis, interhomolog recombination produces crossovers and noncrossovers to create genetic diversity. Meiotic recombination frequency varies at multiple scales, with high subtelomeric recombination and suppressed centromeric recombination typical in many eukaryotes. During recombination, sister chromatids are tethered as loops to a polymerized chromosome axis, which, in plants, includes the ASY1 HORMA domain protein and REC8-cohesin complexes. Using chromatin immunoprecipitation, we show an ascending telomere-to-centromere gradient of ASY1 enrichment, which correlates strongly with REC8-cohesin ChIP-seq data. We mapped crossovers genome-wide in the absence of ASY1 and observe that telomere-led recombination becomes dominant. Surprisingly, asy1/+ heterozygotes also remodel crossovers toward subtelomeric regions at the expense of the pericentromeres. Telomeric recombination increases in asy1/+ occur in distal regions where ASY1 and REC8 ChIP enrichment are lowest in wild type. In wild type, the majority of crossovers show interference, meaning that they are more widely spaced along the chromosomes than expected by chance. To measure interference, we analyzed double crossover distances, MLH1 foci, and fluorescent pollen tetrads. Interestingly, while crossover interference is normal in asy1/+, it is undetectable in asy1 mutants, indicating that ASY1 is required to mediate crossover interference. Together, this is consistent with ASY1 antagonizing telomere-led recombination and promoting spaced crossover formation along the chromosomes via interference. These findings provide insight into the role of the meiotic axis in patterning recombination frequency within plant genomes.

Highlights

Meiosis is a specialized cell division that increases genetic diversity in populations [1, 2]
Previous work has shown that asy1 mutants undergo normal telomere clustering, formation of meiotic double-strand breaks (DSBs) foci during early leptotene, and polymerization of an axial structure marked by REC8 and ASY3 (Fig. 6A) [9, 15, 31]
Using highresolution mapping of crossovers via sequencing F2 plants, we show that recombination becomes largely restricted to a telomere-led zone (TLZ) in asy1 homozygotes (Fig. 6B)

Summary

Introduction

Meiosis is a specialized cell division that increases genetic diversity in populations [1, 2]. During prophase I of meiosis, homologous chromosomes undergo DNA double-strand breaks (DSBs) that can be repaired using an interhomolog pathway, which may result in crossovers or non–crossovers [1, 3]. Genome-wide analyses have revealed that meiotic DSB and crossover frequency are highly variable between the telomeres and centromeres of plant chromosomes [24,25,26,27,28,29]. The zone of telomere-led recombination in asy and asy1/+ corresponds to distal regions of the chromosomes with lowest ASY1 and REC8 ChIP-seq enrichment in wild type. Our data show that ASY1 exerts a major effect on the crossover landscape via mediating interference and acting as a gene dosage-dependent antagonist of telomere-led recombination

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Results

Conclusion