Egg citing amphibians: How frogs have been helping us discover the secrets of DNA

Take a moment to imagine DNA. What do you see?

For most, a number of different images come to mind – maybe the infamous double helix; maybe a zipper; maybe a little hunk of white in a tube from those strawberry DNA extraction experiments you did in second grade. Maybe you even think of the classic X, Y and rod shapes of the chromosomes.

But did you think of frogs?

For some researchers, frogs are becoming as synonymous with DNA as that iconic corkscrew ladder. From 19^th century pregnancy tests to the modern-day nucleoplasmic extract (NPE), frogs are cementing their status as DNA researchers.

Frogs have been used in scientific research as far back as the 1800s. They were developed as a model organism by Lancelot Hogben, who used frogs as a primitive pregnancy test. Hogben discovered, somewhat accidentally, that African clawed frogs (Xenopus laevis) exposed to urine from a pregnant woman would ovulate within hours after exposure. Pretty gross, right? But its rapid results made this the leading pregnancy test across the globe for years.

Years before Dolly the Sheep, John Gurdon showed that cloning was possible by transplanting Xenopus nuclei – the DNA-containing “brain” of the cell – from one egg into another. The recipient egg was then able to develop into a whole adult frog while retaining the traits of the donor. This milestone experiment additionally proved that nuclei from an adult, mature cell could be reprogrammed back into a cell capable of development.

Frogs and their eggs were quickly becoming pioneers in genetic and developmental research.

For single cells, frog eggs are enormous, but to our eyes, they’re exceptionally tiny. A red blood cell is microscopic – you can’t see it with the naked eye. But Xenopus eggs are visible to us. They look like an off-brand caviar coated with a light dusting of mold, or some unfortunately colored silicon beads you’d find in with your vitamins. 

"Xenopus eggs are visible to us. They look like an off-brand caviar coated with a light dusting of mold, or some unfortunately colored silicon beads you’d find in with your vitamins."

-- Elizabeth Ampolini

But the power these tiny cells hold is impressive.

Within those little spheres is contained all the components necessary to produce a frog, primed and ready to explode into development once fertilized. Their size, accessibility and nature make them a powerful tool to explore not only development, but DNA as well.

However, as with any cell, there are certain drawbacks. To access DNA, you must penetrate several protective layers. DNA is the code for life – it’s guarded by several gauntlets of protection. These barriers make mechanistic research on DNA difficult.

But what if you could take the nucleus, the “brains”, out of a cell? What if you could take everything you needed out and leave behind only the guards?

That’s exactly what researchers have done.

Using high-speed separation techniques, Xenopus eggs once again were used to make a NPE – essentially a “cell soup” containing all the necessary components to study how DNA works within the nucleus without all the “guardians.” NPE makes it easy to study all things DNA – how it copies itself, how it’s used to make proteins, how it’s regulated and repaired – without the potential pitfalls of traditional cell culture.

NPE is a powerful tool to study DNA. Here at MUSC, the Long lab uses it to study DNA damage and repair.

“The extract is really versatile; it’s a good compromise between protein biochemistry and cell biology,” says David Long, Ph.D., associate professor in the department of Biochemistry and Molecular Biology at MUSC.

“It’s a really neat system; I don’t know of anywhere else where you can have all of the natural biological processes still occurring in a cell-free setting,” says Julie Dickerson, Ph.D. candidate in the Long lab.

With Xenopus at their side, researchers in the Long lab can ask specific questions about how DNA-based processes are regulated. Currently, the lab studies how DNA damage and repair mechanisms are regulated, and how our cells are able to balance between running multiple processes on DNA at once.

And it’s all powered by frogs!

While they may not be the most classic image that comes to mind, frogs are quickly proving their worth as DNA scientists. Their eggs have shown their importance again and again in DNA-related research. From pregnancy tests to cloning to NPE, their versatility and stability makes them excellent lab assistants. Who knows – maybe one day soon, when people hear “DNA”, their brains will “hop” right to frogs!