MADDIE SOFIA, BYLINE: You are listening to SHORT WAVE...

Hi, shortwave. Maria Godoy and producer Berly McCoy are here.

BERLY MCCOY, connection: Hi, Maria.

GODOY: Ok, Berly, what do you have in your pod today?

MCCOY: I want to talk about the beautiful and extraordinary substances responsible for all the lives we know.

MCCOY: Don't you know nucleoprotein?

MCCOY: It has beauty. There is a mystery. And it has a very long history.

McCoy: Yes. The first article about it was published in 1871, which is 150 years ago this year. It was discovered in Germany by the Swiss scientist Friedrich Michel. At that time, we knew very little about the cell, so he was actually just trying to figure out what was inside the cell.

GODOY: What did he do? How did he find this?

MCCOY: The only logical way-he removes the pus from the used surgical bandage.

Godoy: Oh, my goodness. Burleigh, this is disgusting.

MCCOY: What we do for science.

MCCOY: So Friedrich is doing his experiment. He keeps getting a mysterious mucus, which is definitely not protein. So he finally realized that this was a brand new thing, an undiscovered molecule.

GODOY: Oh, that sounds exciting. Did he find it in the nucleus? Is this why it is called a nucleoprotein?

McCoy: Yes. But now, the nucleoprotein has a new name. I think if I tell you about his later experiment, you might guess its new name. Look, afterwards, Miescher started experimenting with fish sperm.

Godoy: My God. First it was pus, now it was fish essence. are you kidding me?

McCoy: I know, I know. So at that time he began to speculate that nucleoprotein is related to fertilization and inheritance.

Godoy: Oh, my goodness. Is it DNA? Did i win? Ding, ding, ding.

MCCOY: Yes-Ding, Ding, Ding. It turns out that there is a lot of DNA in sperm-right? -This makes sense, because literally, this is their goal in life.

GODOY: I know what you did there. In the show today, we are talking about myths, molecules, legends-DNA.

MCCOY: If you can now look inside the cell, the beautiful long double helix shape that you may already know is not what you see.

MCCOY: This is Berly McCoy.

GODOY: You are listening to NPR's daily science podcast SHORT WAVE.

GODOY: Well, Berly, so we are talking about DNA and deoxyribonucleic acid, which is a bit embarrassing to say.

McCoy: Definitely. As the molecule develops, it is a fairly large molecule.

GODOY: Well, it has an important job. It makes you and me, do you know?

MCCOY: It does constitute you and me. DNA is the blueprint that our cells use to make all the proteins we need to function, from digestive enzymes to the keratin that makes up our hair and nails. I talked about all this with Pravrutha Raman. She is a researcher at the Fred Hutchinson Cancer Research Center. She said that although we are really complicated, our DNA is very simple. It is just four chemical letters.

PRAVRUTHA RAMAN: These are just different combinations of A, T, G, and C. This is the basic part of DNA, which is kind of cool. It has only four nucleotides, which is all that is required to make up all DNA.

MCCOY: So if you remember to learn DNA structure, all these nucleotides are basically like rungs on a ladder...

MCCOY: ...on both sides of the ladder, you know, two long chains of alternating sugar and phosphate molecules. Then the two strands are wound around each other to form the iconic double helix shape.

GODOY: Okay, but, Berly, not too long ago, you told me that if I could now take the magic school bus into my cell nucleus, I would not see a long string of double helix DNA. So what to give?

McCoy: I know, I know. Thoughts are being blown away. But there are good reasons for this. If you take all the DNA from just one cell and stretch it, its height will exceed 6 feet.

GODOY: Berly, I'm only 5 feet 4 inches when the weather is good. Like, how do I get 6 feet of DNA in my body?

McCoy: I know. It's not even just your body-in a single cell.

Godoy: Wow. This is a lot of DNA in a small living space. So how do we stuff so much information, for example, such a long thing into a tiny single cell?

MCCOY: Maria, very accurate, because we still need to be able to use it all the time. Packaging our DNA is actually a super organized and complex process. This is what Pravrutha is studying-how DNA is compressed into the nucleus of our cell, which is only about 10 microns wide. This is a hundred times smaller than a grain of sand.

GODOY: All my 6 feet of DNA is contained in it. For example, what does this look like?

MCCOY: I asked Pravrutha the same thing.

Raman: So the double helix is ​​actually more tightly packed in a unit. So we have some proteins, the DNA is wrapped around these proteins, and it is very beautifully called the beads on the string. Each bead is composed of these histones. Then the rope wrapped around the beads or between the beads is the DNA double helix.

GODOY: I haven't taken biology classes for several years, so remind me; these beads, these histones-what are they?

McCoy: Yes. Essentially, their entire job is to help organize DNA. In fact, with the development of proteins, histones are ancient. Pravrutha told me that we basically have the same histones as yeast, and we parted ways with yeast on the evolutionary tree more than 1 billion years ago.

Godoy: Wow. So if evolution has not changed them, I guess it must mean that they are really important, right?

Raman: These proteins are absolutely necessary. You cannot delete them. If the histones are lost, all cells have died.

MCCOY: So basically, these histones act as a spool of thread, in this case DNA.

MCCOY: And because our DNA is negatively charged, and these histones are positively charged, they attract each other, which helps to compress the DNA.

Raman: Then these beads can be very close or far away from each other, which helps with tighter or looser packaging.

MCCOY: Pravrutha said that scientists are still trying to understand the more layered organization of beaded strings.

GODOY: It's really a bit smart, a bit magical, it can all be there.

GODOY: Okay, but this is my question. If DNA is a blueprint and our cells need to read the blueprint to make us, then if all DNA is packaged like this, how can our cells read our DNA?

MCCOY: This is what's really interesting, Maria. Pravrutha told me that different types of packaging change the way DNA accesses our cells. So, like, DNA that is really tightly packed is inaccessible, and this is where our star protein histones come in.

Raman: These histones can be used to change the accessible or inaccessible parts of DNA. Basically, every time you want to access the DNA fragments bound by these beads, you can either-expel the beads or remove the beads or move the beads to make the DNA more accessible.

MCCOY: So our cells have been busy processing a million jobs, but these jobs will change. Like, if a cell is about to divide, it needs to read different parts of DNA. According to the needs of the cell, it will send different signals to tell the tightness of the histone packaging DNA, and then control which parts of the DNA can be read.

GODOY: So these histones wrapped in DNA, they are, like, very powerful, because they actually control which parts of the DNA can be read, right?

GODOY: That's really cool. This will definitely affect many things that happen in the cell.

Raman: So, if you consider developing or observing different cells, you would want to make different proteins in these different cells.

MCCOY: Your muscle cells need to read different parts of the blueprint, not the cells in your tongue or the cells in your lungs, which are controlled by histones. So the DNA in our cell nucleus is actually a mixture of ultra-compact and ultra-loose DNA, depending on the needs of the cell at the time.

GODOY: Ok, Berly, so I got what the DNA in the cell looks like-very organized beads on string. I understand why it is organized this way. But I have a more poetic question for you.

GODOY: (Imitating British accent) Berly, how can this tiny rope complicate you and me so much?

MCCOY: (Laughter) Okay, this is shocking-right? -Especially because the DNA code is very simple. So to describe how our DNA shapes us, Pravrutha starts from the beginning

Raman: So we all started with single-cell embryos. Then you continue to make skin cells, blood cells, and heart cells. So in order to make every cell, you have to visit different parts of the DNA to make the protein you want, so that the cell can become what it ultimately wants to be.

MCCOY: These cells constitute tissues, and these tissues constitute organs. This is quite an amazing process

Raman: It’s crazy to me to start with something simple, but to be able to make something truly complex in the end, using all the functions together as a cohesive unit.

MCCOY: However, if you think about it, the miracle of the human body is also amazing.

Godoy: Yes. Thank you, DNA. Thank you, Berly, for bringing this story to us.

GODOY: This episode was produced by Eva Tesfaye, edited by Rebecca Ramirez, and checked by Margaret Cirino. The audio engineer is Stu Rushfield. This is Maria Godoy. Thank you for listening to NPR’s daily science podcast SHORT WAVE. Not to mention it for now.

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