What Limits Meiotic Crossovers?

Crossing over (CO) at meiosis is necessary for a balanced meiotic division. The number of crossovers is tightly regulated, with a narrow variation of number per cell and per chromosome. Many factors required to promote crossovers have been identified, including ZMMs, a series of proteins essential for the main CO pathway in most species, and MUS81 involved in a lesser used pathway. However the factors that limit the number of crossovers remain largely unknown. Here, we designed a screen specifically to identify anti-CO genes, based on restoration of fertility of Arabidopsis zmm mutants. We thus identified a series of mutation increasing CO formation, and identified the corresponding gene. Strikingly, the mutant showed a three-fold increase of meiotic recombination frequency compared to wild-type. Our data show that these extra CO arise from a ZMM-independent pathway: (i) The mutation dramatically increases CO frequency in all zmm mutants tested. (ii) CO interference which shapes ZMM-dependent CO distribution, does not affect the extra-CO. (iii) The extra-CO are not associated with MLH1, a marker of ZMM-dependent CO. (iiii) In the mutant context, MUS81 is required for the completion of meiotic recombination. Thus, we identified one major factor imposing upper limits on the number of meiotic crossovers, by limiting a normally minor pathway. This finding supports the idea that natural selection constrains crossovers below their possible maximum at a specific equilibrium between the long-term advantages and costs of recombination. Furthermore manipulating this gene, which is very conserved in eukaryotes, holds great promise for increasing recombination frequency in plant breeding programs.