Biologists have a habit of using so-called “model organisms” to study biological phenomena that interest us. We throw this term around a lot. In my particular field of cell biology and in related fields of genetics and developmental biology, we use a lot of interesting and strange model organisms. So what is a a model organism, anyway? We use model organisms when we want to study something about human biology, but would rather not perform our experiments on another human. Instead, we turn to organisms we find around us that are similar to us in ways that are relevant to the question we are studying, and whose genome is perhaps known so that we can study the function of genes and compare them to human genes. Importantly, key metabolic pathways and genetic interactions are evolutionarily very well conserved between us and our distant relatives. This is why it is possible to study how cell division works in Saccharomyces cerevisiae (brewer’s yeast), for example, and actually learn something about how our own cells work.
Maybe I’ll spend some more time talking about the use of brewer’s yeast or other common model organisms like Drosophila melanogaster (fruit flies) or Mus musculus (field mice) in a future post. But today I would like to highlight a more unusual model system: giant newt chromosomes, which are found in cells from the lung of the newt species Notophthalmus viridescens.
I first heard about this model system at the American Society for Cell Biology meeting this past December in New Orleans. The biophysicist John Marko studies the structure of chromosomes, and it turns out that the cells from this species of newt are very useful for this, because their chromosomes are huge. The largest human chromosome is about 250 megabases (Mb) (or 250,000,000 bases) long, while N. viridescens chromosomes average 2 gigabases (Gb) (or 2,000,000,000,000 bases) long. Because of the way that DNA is packaged to form the chromosome, this means that a condensed human chromosome is about half as long and wide as a newt chromosome.
John Marko and his colleagues took advantage of the larger size of newt chromosomes to do something kind of amazing. First, they put the living cells on a microscope. Then, they watched and waited until a cell went into mitosis. When cells go into mitosis, the chromosomes condense into the most tightly packed structure they can manage (the roughly X-shaped structure in bottom of the diagram above), so that they can be efficiently organized and separated into the two daughter cells. The scientists then took a tiny glass micropipette and broke the nucleus open, freeing the chromosomes. They then pulled one of the chromosomes out using the pipette. You can see all this happening in this movie from Dr. Marko’s website. Unfortunately I can’t post the whole movie here (but you should go check it out), so here are some time lapse images from the movie:
Ok, so they are able to extract these giant chromosomes individually. Then what? And for what purpose? The Marko lab takes these individual chromosomes and pulls them apart to see how much force they can withstand. They use this test to learn how the chromosome is assembled and scaffolded by proteins. If you look at a cell going through mitosis, you’ll notice that the chromatin condenses into dense, tubular structures as the cell progresses into mitosis. If you were to stretch the DNA from each chromosome out linearly, it would be a few centimeters long. But when it’s compacted and organized into a mitotic chromosome, it’s only about 20 microns (that’s 0.000 02 centimeters) long! That is an impressive packing job. It’s kind of like starting with this:
and organizing it into this:
The nucleus is a very crowded place, and how all of those chromosomes manage to untangle themselves and get separated efficiently in each round of cell division is still something of a mystery. I am a knitter, and when my yarn stash looks like the former image, it takes me hours to get it cleaned up and looking like the latter image. Chromatin, on the other hand, condenses into easily maneuverable mitotic chromosomes in minutes.
Sun M et al Phys Biol 2011
Marko JF Chromosome Research 2008