Zooming In on Meiosis

Posted on December 6th, 2018 by Dr. Francis Collins

Credit: Simone Köhler, Michal Wojcik, Ke Xu, and Abby Dernburg, University of California, Berkeley

Meiosis—the formation of egg and sperm cells—is a highly choreographed process that creates genetic diversity in all plants and animals, including humans, to make each of us unique. This kaleidoscopic image shows cells from a worm exchanging DNA during meiosis.

You can see a protein-based polymer tether (green) from what’s called the synaptonemal complex. The complex holds together partner chromosomes (magenta) to facilitate DNA exchange in nuclei (white). Moving from left to right are views of the molecular assembly that progressively zoom in on the DNA, revealing in exquisite detail (far right) the two paired partner chromosomes perfectly aligned. This is not just the familiar DNA double helix. This is a double helix made up of two double helices!

The image, one of the winners of the Biophysical Society’s 2018 Art of Science Image Contest, comes from the NIH-supported lab of Abby Dernburg at the University of California, Berkeley. To capture this award winner, Simone Köhler, then a postdoc in the lab, used two super-resolution imaging techniques: photo-activated localization microscopy (PALM) and stochastic optical reconstruction microscopy (STORM).

These breakthrough approaches create a very high-resolution image that records the position of individual proteins within a cell. Working in collaboration with the lab of Ke Xu, also at UC Berkeley, Köhler combined both methods to map out the molecular architecture of the synaptonemal complex, as well as to see how it changes during the process of DNA exchange [1].

All photographic beauty aside, this work and other projects in the Dernburg Lab have led to a surprising result: the synaptonemal complex behaves as a liquid crystal, an intermediate phase of matter in which molecules have a regular organization but can move freely [2]. This unique material assembles between paired chromosomes as they interact and holds them at a fixed distance. More amazingly, the results suggest that the synaptonemal complex acts as a “highway” for biochemical signals to travel rapidly along chromosomes. Thus, this information flow controls both the spacing and the number of DNA exchanges between paired chromosomes.

This work on the dynamics of chromosome-chromosome interactions is a great example of the value of basic research. Errors in meiosis are the leading known cause of miscarriage and a frequent cause of developmental disabilities. But seeing meiosis at this super resolution also conveys a sense of awe at how this life-giving process contributes to making us all unique.

References:

[1] Superresolution microscopy reveals the three-dimensional organization of meiotic chromosome axes in intact Caenorhabditis elegans tissue. Köhler S, Wojcik M, Xu K, Dernburg AF.. Proc Natl Acad Sci U S A. 2017 Jun 13;114(24):E4734-E4743.

[2] The synaptonemal complex has liquid crystalline properties and spatially regulates meiotic recombination factors. Rog O, Köhler S, Dernburg AF. Elife. 2017 Jan 3;6. pii: e21455.

Links:

Meiosis (National Human Genome Research Institute/NIH)

What are Liquid Crystals (Kent State University, Kent, OH)

Dernburg Lab (University of California, Berkeley)

Köhler Group (European Molecular Biology Laboratory, Heidelberg, Germany)

Ke Xu Group (UC, Berkeley)

The Art of Science Image Contest (Biophysical Society, Bethesda, MD)

NIH Support: National Institute of General Medical Sciences