21: Cracking Life’s Code

Last episode, we were floating in Earth’s earliest oceans, more than 4 billion years ago. We saw small molecules link together into larger shapes, boosted every now and then through lightning strikes. Similar conditions have been reenacted in laboratories by scientists, forming sugars and acids out of air, water and a tiny push of energy. This is the famous primordial soup, but as I have stressed many times, it ain’t alive just yet.

At this point, you might throw your hands in the air, crying out:

“Dylan, just get to the point! We’ve spent five episodes, more than an hour inching towards life, but not getting there. I thought this was a geology podcast, not a biology one. What gives?”

That’s a fair question with a few answers. First, I’ll admit I’m personally biased. I’m a geobiologist by trade- a paleontologist looking for fossil pond scum. If this podcast was made by a volcano expert, they might spend 5 episodes on tectonics, and just one or two on life.

However, I truly think the question “How did life begin?” is objectively one of the most important in all science. To answer it, we need to break it into smaller topics, like “What’s life made of?” and “How did these pieces come together?”. Finally, this is my show, I can set my own schedule.

But, for those itching to move on, here’s a gameplan: after this episode, there will be two more on life’s origins. Today, we’ll make the first DNA, the code of life. Next episode, we’ll make the first cells. Finally, we’ll bring it all home and make the first living thing on Earth.

With that in mind, let’s dive back into the Hadean sea and learn just how DNA got started.

Part 1: The Two Sisters

DNA is one of the most famous molecules, for many reasons.

First, and most importantly, every living thing on Earth, from bacteria to Bruce Springsteen, makes DNA. If something isn’t making its’ own DNA, it’s either dead, or was never alive at all.

Second, DNA is big for a molecule. Ludricously big. For reference, the longest protein in your body is a fraction of a human hair. In contrast, if you take just one molecule of DNA and stretched it to its’ full length, it would be 2 meters or 6 feet long- the length of a human body.

How can that be? How can these gigantic molecules of DNA fit in every single cell in our body? DNA might be long, but it’s very, very thin, 10,000 times thinner than a human hair. DNA’s shape also helps pack it in, which is another reason why it’s famous.

A single molecule of DNA looks like a tangled, coiled mess of string. If you pulled the big knots apart, you would see smaller, tightly wound coils, like an old telephone wire. Repeat this process with smaller coils, and you begin to see how DNA can pack so much into so little space. 

After you pick every knot and coil apart, the basic shape of DNA is a twisted zipper, with horizontal teeth stretching between two curved rails on either side. This shape is the famous double helix.

Just like a zipper, DNA can be torn straight down the middle into two long chains of teeth. Pay attention to these teeth- they are the building blocks of DNA, and they are called nucleobases, we’ll call them bases for short. Bases come in four flavors- we don’t need to know their names, but you’ve probably heard their nicknames- the letters A, C, G, and T.

So far, we’ve only discussed DNA’s shape, but what exactly does it do?

The bases in DNA are a code, a library, a recipe, an instruction manual all wrapped up in one tight package. Specifically, DNA provides the blueprint for turning tiny amino acids from Frank Miller’s experiments into complex proteins such as turkey meat. It’s the next step towards life.

However, DNA alone isn’t enough. If you put the DNA code for turkey meat right next to a huge pile of amino acids like tryptophan, absolutely nothing would happen. It’s like setting a recipe for cake next to eggs, sugar, and flour and waiting for cake to magically appear.

There needs to be a bridge between the two- a molecule that can both read DNA’s recipe and get its’ hands dirty with amino acids. Fortunately, we don’t have to search far. Meet DNA’s little sister- RNA.

DNA and RNA are very similar, yet worlds apart. Both are made from long strings of nucleobases, and both contain codes for making proteins. In fact, DNA can be directly transcribed into RNA, and vice versa. Their languages are nearly identical but slightly different, like Spanish and Portuguese. 

The most important difference is that RNA only has one set of bases, one set of teeth. Imagine RNA as half a zipper instead of DNA’s full set. Half a zipper might sound useless, but it actually makes RNA a lot more flexible and versatile. For example, a single strand of RNA can fold back and connect with itself multiple times, forming demented train tracks that would be impossible for DNA to make. These shapes not only look cool, they can be used as tools, breaking other molecules apart or forging them together.

RNA’s flexibility also makes it a popular molecule to play with. Its’ most common friends are amino acids and proteins. And now we can start to imagine how RNA might form a missing link between its’ passive sister DNA and complex proteins. To recap: RNA can be copied from DNA, hangs around amino acids, and has the power to shape molecules. It’s the perfect storm to make something new.

While DNA is more flashy and famous, RNA does far more of the actual work for a lot less credit. Perhaps you know the feeling.

So how does RNA make turkey meat and other complex proteins using DNA’s code?

Part 2: The Recipe, The Chef, and The Assistant

As a child, I would often help my mom bake in the kitchen. Mom would read the recipes out loud, I would run around the kitchen and collect the ingredients, then she would mix it together into something delicious.

Inside a cell, RNA does something similar, playing the role of the recipe, the chef, and the assistant. To be clear, it’s not the same molecule of RNA doing everything, there are three different actors here.

From left to right, RNA in its’ roles as the “Recipe”, the “Assistant”, and the “Chef”

The Recipe RNA is a long, straight half-zipper, a direct copy of DNA. No frills, no funny business, simple straightforward code.

The Chef RNA is a large, dense, tangled mass, hunched over the Recipe, reading it closely. As it pores over the various As and Cs and Gs, it summons the Assistant RNAs. These Assistants are a cloud of small RNA molecules floating around the cell. On one end of each Assistant is a password that matches a specific word of the Recipe’s code. On the other end is an amino acid, an essential ingredient for larger proteins.

For example, when the Chef calls out GGG, an Assistant comes running up with a single shot of glycine, a sweet amino acid. The Chef takes the glycine, pats the Assistant on the head, sends it on its way, and calls out for UGG next for tryptophan. The Chef links the glycine and tryptophan, and so on, building a long protein from tiny amino acids. Finally, the recipe tells the chef to stop, and everyone goes on their merry way.

I’ve made this sound like a chill Sunday kitchen at home, but in reality, we’re talking fast food. The Assistants can deliver 20 amino acids to the chef every second, building huge proteins in under a minute.

Of course, the Recipe, the Chef, and the Assistants aren’t the real names of these RNA actors,  but this is a geology podcast, so I think it’s safe to gloss over the gritty details. Perhaps I’ll have a biologist on to talk about it in greater detail.

This has been a dense episode so far, so let’s step back and soak this all in. DNA is the code for life- specifically, it’s the code to make complex proteins from simple amino acids. RNA does the heavy lifting- transcribing code, gathering ingredients, and building the actual proteins. The whole ordeal is complex and took many years of research to figure out. One of the key questions left, bringing us back 4 billion years ago is this: how did this intricate assembly line get started in the first place? 

Part 3: RNA World

Which came first, the chicken or the egg? This simple schoolyard question was a huge puzzle for thousands of years, since Aristotle. To ancient and medieval thinkers, it seemed like one could not exist without the other. In modern science, there is a clear answer: the egg, since many animals were making eggs long before the first chickens.

There was a similar debate in biology between DNA and proteins. DNA is literally the code for proteins, so you would expect it to come first. Yet, many of the cells’ functions that protect and maintain DNA involve proteins, suggesting an earlier origin. Unlike the chicken and the egg debate, this argument has a third option: neither DNA nor proteins came first. Instead, it was our newest friend, RNA.

Remember, RNA already has the code for making proteins, and it has the power to directly make them, which DNA can’t do by itself. While RNA looks like the middleman between DNA and proteins, this position makes it invaluable, and a good contender to be the earliest piece.

The idea that RNA formed before DNA has been around since the 60’s, becoming more popular over the decades. The idea even has its’ own name: “RNA World”, like a much nerdier version of Jurassic Park.

The term RNA World has become shorthand for ancient Earth just before life. If RNA came first, how did it start?

Like most things in the Hadean, it starts in outer space. When we crack open carbon-rich meteorites, we find nucleobases, the building blocks of RNA and DNA forged in space. Alternatively, bases could have formed right here on Earth’s surface. The Miller-Urey experiment from last episode did not make nucleobases, but it didn’t take long for Spanish scientist Joan Oro to make the letter A for adenine under similar conditions. Since then, many others have forged RNA’s alphabet, but no one has re-made RNA itself, the poetry of life.

What we think happened is this: in the Hadean, in the primordial soup, a few nucleobases would bump into each other, holding steady and slowly growing into longer strings. Some of these strings would form new and more stable shapes. A few of these shapes were very useful as tools, manipulating other molecules in the soup, and even making more RNA copies. As I write this, I’m struck by the similarities with our planet’s earliest days, as the Earth grew larger from many tiny pieces. From small things, big things grow.

One possible way “RNA World” took simple molecules and built complex structures

In 2023, RNA World is the top contender for an Earth just before life, but there are still many unanswered questions. When and how did DNA show up after RNA? How did the complex chain between these two sisters start? And where do viruses fit in, which have DNA and RNA, but are not alive? Unfortunately, none of these molecules survive in ancient rocks or crystals, so future answers will have to come from some creative problem-solving. But if there’s anyone up to the task, it’s the Hadean research community. When they come up with an answer, you’ll be the first to know.

Summary:

DNA and RNA are incredible organic molecules, with nothing else like them on Earth. Both are made of smaller nucleobases, the code for making proteins. DNA lists the recipe alone, while RNA can also dish it out. Our best guess is that RNA formed first in the Hadean, more than 4 billion years ago, slowly building and changing in the primordial soup. One of science’s greatest mysteries is how RNA linked up with DNA and proteins to kickstart life’s great chain. For now, we’ll move on to the final piece of life’s puzzle- how did these complex molecules get rounded up together inside the first cells?