Shared Meiosis Proteins Take On Different Roles Across Animals, Stowers Study Finds

At a microscope at the Stowers Institute for Medical Research, Stefanie "Steffi" Williams looked at sea anemone cells in which certain proteins had been knocked out, and saw chromosomes pairing up anyway. She thought she must have made a mistake. By her account, it made no sense: those proteins were supposed to be needed for the job.

The work, published in Science Advances, concerns meiosis, the process by which egg and sperm cells are made. Chromosomes find their partners, swap genetic material, and then divide. When the process fails in humans, the results can include infertility, miscarriage, and birth defects. The Stowers study shows that the molecular machinery behind it is more widely shared across animals than expected, and also more flexible than expected.

Williams, a Stowers Graduate School alum now a postdoctoral fellow at the European Molecular Biology Laboratory, led the project. It grew out of a collaboration between the lab of Stowers Investigator and Graduate School President Matt Gibson and the lab of the late R. Scott Hawley, a former Stowers Investigator and a pioneer in meiosis research. Her subject was Nematostella, a sea anemone related to corals and jellyfish, which is the focus of Gibson's research.

Williams found that the sea anemone builds a ladder-like structure called the synaptonemal complex between paired chromosomes, much as humans do. The structure includes eight of the ten proteins known to make up the human version. On that evidence the two systems looked close to interchangeable. Testing what the proteins actually do, however, showed the resemblance breaking down.

She disabled three of the proteins. Mutations in two of them, sycp1 and syce2, caused female sterility, while males with the same mutations stayed fertile. Loss of syce2 disrupted the stabilization of paired chromosomes only in females. Some components, meanwhile, turned out not to be required for chromosomes to synapse at all. Williams said that finding the architectural functions of these proteins must have changed was totally unexpected.

She had reason to be curious. Many proteins that coordinate meiosis show signatures of rapid evolution, changing much faster than normal housekeeping genes. Older research had shown that cnidarian genomes encode proteins clearly similar to human ones, and she wanted to know whether they truly worked the same way. Gibson described the broader lesson: proteins and protein complexes may look very much the same yet function in different ways.

There is also a practical payoff. Until now, functional studies of these proteins in animals were largely limited to mice, fruit flies, and roundworms. Nematostella is transparent, and its eight gonads can be observed directly in live animals, which opens the possibility of watching meiosis unfold in living tissue. Gibson said this establishes the anemone as a good experimental system, and that live imaging could reveal biology that is hard to see in mammals, particularly at the cellular level.

The project's origins were personal as well. Williams first rotated in the Hawley Lab, studying meiosis in the fruit fly Drosophila, then rotated into Gibson's lab and began working with Nematostella. Gibson said Hawley inspired her passion for meiosis, and that he felt lucky to benefit from Hawley's knowledge and her excitement. Williams said Hawley taught her to follow her passion regardless of what others think, and the importance of teaching and good mentorship.

What to watch next is whether live imaging of the anemone's gonads begins to answer questions about chromosome behavior that mammals make difficult to ask.