How sex cells get the right genetic mix: An interdisciplinary approach solves a century-old puzzle

Super-resolution microscopy images of an Arabidopsis meiotic cells showing DNA in blue, ZYP1 and ASY1 respectively. Credit: John Innes Centre New research reveals what factors determine the position and number of genetic exchanges in sex cells. This includes pollen and eggs for plants and sperm and eggs for humans. Meiosis is a special cell division that produces sex cells. It involves large DNA segments being exchanged by chromosomes. This allows each cell to have a unique genetic makeup. It is why, except for identical twins and other siblings, no two siblings are ever exactly the same genetically. These DNA exchanges or crossovers are crucial for the generation of genetic diversity. Their frequency and location along chromosomes is tightly controlled. Chris Morgan, co-first author of this study, explains the significance: "Crossover placement has important implications for evolutionary, fertility and select breeding. Understanding the mechanisms behind crossover positioning will make it easier to find ways to modify crossover positioning in order to improve existing plant and animal breeding technology. Over a century of research has not revealed the mechanism behind cross-overs. This puzzle has both fascinated and frustrated many prominent scientists. Crossover interference was first coined in 1915. It refers to the observation that a crossover at one place on a chromosome inhibits the formation nearby. John Innes Centre researchers solved this century-old mystery using a combination of mathematical modeling, super-resolution microscopy and '3D SIM' super-resolution microscopy. They discovered a mechanism that ensures that the numbers and positions of crossovers are just right: not too many, too few, and not too close. The behavior of a protein called HEI10, which is involved in meiosis crossover formation, was studied by the team. Super-resolution microscopy revealed HEI10 proteins cluster along chromosomes and initially form many small groups. As time goes by, the HEI10 protein clusters become smaller and more concentrated. This can lead to crossover formation once they have reached a critical mass. The measurements were then compared with a mathematical model that simulates clustering. It is based on diffusion of HEI10 molecules, and simple rules for clustering. The mathematical model was able to explain and predict many experimental observations. This included the fact that crossover frequency can be modified reliably by changing the amount of HEI10. John Fozard, co-first author, explains: "Our study showed that super-resolution images from Arabidopsis reproductive cell cells are consistent with a mathematical "diffusion-mediated coarsening" model for crossover patterning. This model allows us to understand how crossovers occur along meiotic DNA chromosomes. This work continues the John Innes Centre tradition of using plants to study fundamental and conserved aspects of genetics. J.B.S Haldane, a JIC alumni, and Cyril Darlington studied the same process in the 1930s. Robin Holliday, another JIC alumni, predicted similar results using the model. Professor Martin Howard, the correspondent, says: "This work is an example of interdisciplinary Research, where cutting-edge experimental and mathematical modeling were both required to unlock the core of the mechanism. Future research will examine whether our model can be used to explain crossover patterns in other organisms. This research is especially valuable for cereal crops like wheat, where crossovers are usually restricted to certain regions of the genomes. This prevents plant breeders from obtaining the full genetic potential of these crops. Nature Communications published "Diffusion-mediated HEI10 sanding can explain Arabidopsis' meiotic crossover positioning" Continue reading The regulation of meiotic crossing in plants More information: Diffusion mediated HEI10 coarsening may explain meiotic crossing positioning in Arabidopsis. Nature Communications (2021). Information from Nature Communications Diffusionmediated HEI10 coarsening in Arabidopsis can explain meiotic crossing positioning, (2021). DOI: 10.1038/s41467-021-24827-w

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