A compartmentalized signaling network mediates crossover control in meiosis

Most human cells contain 23 pairs of chromosomes, giving 46 chromosomes in total. When a cell divides, it typically copies all its chromosomes and distributes the copies equally between the two new cells, so that they also have 46 chromosomes. Cells in the reproductive organs undergo a special division process called meiosis, which halves the number of chromosomes. As a result, sperm and eggs have just 23 chromosomes, and so when they combine, the fertilized egg receives a complete set of 46 chromosomes. A similar process happens in all species that use sexual reproduction. As the chromosomes prepare to separate, they line up side by side in matching pairs. During this period, DNA from one chromosome will swap with DNA from its partner. These events are called “crossovers,” and because such exchanges can happen at many locations along the chromosomes, no two sperm or eggs are the same. Historic studies in fruit flies revealed that chromosomes do not mix their DNA at random. After one crossover occurs, it is less likely that another will happen, and if there are two crossovers, the second one tends be far away from the first. This suggests that there must be a signal that tells the chromosomes about the exchange. However, the nature of the signals and how they are communicated along pairs of chromosomes remain mysterious. A structure called the “synaptonemal complex” holds chromosomes together while they mix their DNA. In 2017, researchers found that this structure behaves like a liquid crystal: its molecules are organized into a regular, repeating pattern, but they move freely, like a fluid. If signals could move through this material, this might explain how information spreads along paired chromosomes. Now, Zhang et al. – including two researchers involved in the 2017 work – identify some of the signals in the small roundworm, Caenorhabditis elegans, as four related proteins named ZHPs. When tagged with fluorescent markers and followed under a microscope, all four ZHP proteins moved to the liquid crystal-like synaptonemal complex during meiosis. Depleting the proteins at this crucial time revealed their roles. Two of the proteins are needed for chromosomes to mix their DNA, while the other two control the number of exchanges between each pair of chromosomes. Successful meiosis depended upon all four ZHPs, and so too did the fertility of the worms. The next step is to find the other molecules that interact with the ZHP proteins during meiosis. Since similar proteins appear in other species, including humans, this could help to reveal more about how genetic traits from our parents mix and match. In the future, studies that build on these findings could also help scientists to understand how errors in these processes give rise to birth defects and infertility.