Crossover interference: Just ZYP it

More than a century ago, research in Drosophila discovered fundamental mechanisms of inheritance that apply to sexually reproducing organisms (1). One key observation was that in meiosis, the cell division that generates sex cells, homologous chromosomes make large-scale reciprocal exchanges of genetic material called crossovers. A second observation was that these crossovers are not randomly distributed, with the presence of one crossover reducing the likelihood of another crossover nearby. This phenomenon, termed interference, results in crossover spacing that is more uniform than expected by chance. To this day, the mechanism of crossover interference remains largely unexplained. In PNAS, Capilla-Pérez et al. (2) and France et al. (3) make a leap forward in our understanding of this puzzling phenomenon.

Meiotic crossovers are formed during prophase I within a highly organized chromosome structure. First, the two sister chromatids of each chromosome are tethered to a proteinaceous axis (Fig. 1). Second, homologous chromosome axes are “zipped” together by a highly ordered and evolutionarily conserved structure: the synaptonemal complex. A repeating unit of the synaptonemal complex, which is analogous to the teeth of a zipper, is the ZYP1 protein, also called the transverse filament. In PNAS, Capilla-Pérez et al. (2) and France et al. (3) leverage the genetic tools available for the plant Arabidopsis thaliana to elucidate the role of the transverse filament in crossover interference. Genetic studies of the transverse filament had been largely precluded in Arabidopsis because it is encoded by an inverted duplication of the ZYP1 gene separated by 2 kb, which was nearly impossible to knock out in the pre-CRISPR/Cas9 era.