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Nematode proteins shed light on infertility


We have two copies of each chromosome in every cell in our bodies except in our reproductive cells. Sperm and egg cells contain a single copy of each chromosome with a unique mix of genes from our parents, an evolutionary trick to give our offspring genetic variability. The sperm and egg are made during meiosis, the process by which cells with two chromosome copies reduce their chromosome numbers to one. For meiosis to work, the two chromosomes must align perfectly and exchange the correct amount of genetic information. Any deviation puts fertility at risk.

Enter the synaptonemal complex (SC), a zipper-like protein structure that lines up and anchors the two parental chromosomes together, end-to-end, to facilitate successful genetic exchanges. Failure to regulate this exchange is a leading cause of age-related infertility in humans and could compromise fertility across the tree of life. Humans, fungi, plants, worms and anything that reproduces sexually uses the SC to make reproductive cells, known as gametes. Despite its importance, we don’t understand how proteins within the SC regulate chromosomal interactions because this multi-step process happens in internal organs and has been impossible to recreate in a lab.

In a new study, University of Utah biologists developed a method for illuminating the intricate interactions of the SC in the nematode C. elegans. The authors identified a trio of protein segments that guide chromosomal interactions, and pinpointed the location where they interact with each other. Their novel method uses a technique known as genetic suppressor screening, which can serve as a blueprint for research on large cellular assemblies that resist traditional structural analysis.

“This is a way to lock in on systems in cells that are too ‘loosie-goosey’ to use methods that rely on crystallization,” said Ofer Rog, associate professor of biology at the U and senior author of the study. “A lot of the interactions in cells are loosely bonded together. The problem is that you can’t look at it under an electron microscope because nothing is stable enough—everything is constantly moving. Our approach allows you to study even the interactions that are relatively weak or transient.”

The study published on Dec. 6, 2023, in the journal Proceedings of the National Academy of Sciences (PNAS).


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