How do squids change their own DNA?

When you edit DNA, it’s permanent. The cell you edit will be changed forever, or at least until it dies. But what if there was a less-permanent way to edit genes? 

There is, actually. It’s called RNA editing and it happens quite a bit in our own cells. RNA is the go-between in protein synthesis. DNA codes to RNA, which then codes to specific proteins. Proteins are what we’re all about, so if you alter anything in that production chain, you can potentially change the entire organism. In nature, RNA editing happens in that stage between DNA and protein synthesis. Here’s how it works:

Imagine protein synthesis: DNA unravels and pairs up with messenger RNA. That RNA breaks off and goes to assemble some protein. Before it can, some sneaky enzymes jump in and make some changes to the RNA. Thanks to those changes, the RNA makes a new protein—one that isn’t coded in the DNA. 

Why would this happen? Multicellular organisms like you and me are super complicated. We require lots of different kinds of proteins to function—more than our DNA actually codes for, in fact. RNA editing is a way to get more variety out of a limited amount of DNA. It gives us more adaptability.

For example, we’ve found that liver and intestinal cells share the same DNA for a particular protein, yet make different versions of it. In the liver, the protein carries cholesterol in the bloodstream. In the intestine, thanks to some RNA editing magic, a shortened version of the protein absorbs lipids—like a fat sponge—before they move into the bloodstream. Same DNA, different protein.

Last episode I said we’d be talking squids. Scientists at the Marine Biological Laboratory in Woods Hole, Massachusetts discovered this RNA editing in squids a few years back. An article published in Wired in May suggests that the discovery was recent, but Joshua Rosenthal and his colleagues announced their discovery in March, 2019. At any rate, they found this kind of RNA editing in squid axons—the long skinny filament-like cells that connect neurons in the brain and nervous system. It’s the first time anyone has seen so much of it. They estimate that more than 60,000 cells in the squid’s brain use RNA editing, giving them a tremendous amount of adaptability. 

Is this even more evidence that cephalopods are from another planet? Or perhaps they are actually earth’s supreme species, more advanced than us talking monkeys. But probably not. They are definitely more well adapted to life in the ocean, and they may be more genetically complex, but they’re not more advanced. In fact, the term “advanced” is meaningless in evolutionary terms. There are just too many factors to measure. Are we talking smarter? Or better at adapting to the environment? If it’s smarts, we win. But bacteria win when it comes to adapting to their environments, no contest. 

But I digress. 

Rosenthal and his colleagues hope to figure out how RNA editing works in squids so they can do the same thing in other animals and humans. Like some kind of Island of Dr. Moreaux scenario? Not really. Many genetic diseases could be treated with RNA editing. And because you’re not changing cell DNA, your changes wouldn’t be permanent.

Wait, wouldn’t you want to permanently fix a genetic disorder? We simply don’t know the long-term effects of modifying DNA directly. A DNA treatment could reverse a genetic disorder, but cause cancer down the line. We just don’t know. RNA editing, on the other hand, would be safer. If doctors encountered any issues with the treatment, they could stop right away without causing permanent damage. 

“RNA editing is a hell of a lot safer than DNA editing. If you make a mistake, the RNA just turns over and goes away,” said Rosenthal in the Wired article.

You can read the article by Eric Niiler at Wired.com, and you can learn a ton more about RNA editing at Chemical Engineering News. Links in the show notes. 

I also found an awesome YouTube channel that delves into the nitty-gritty of RNA editing.  Shomu's Biology goes over RNA editing in a clear and concise manner, using nothing but a headset and a white board. I was definitely able to follow along, even with only half a dozen college biology courses under my belt. Go check him out if you want to nerd out about RNA editing and biology.