Science Friday
Hosted by Flora Lichtman and Ira Flatow
Geneticists mapping nightshade genomes used CRISPR gene editing to grow bigger fruits without sacrificing flavor.
4,248 words · 7 speakers
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Hey there, it's Ira Flatow, and you're listening to Science Friday.
Today on the podcast, how scientists are taking genes from eggplants to make bigger tomatoes.
The modern tomatoes took hundreds of years to develop from the wild species, and now we can do it basically in one generation.
It's that time of the year when I'm planting what's going into my garden, and just to be honest, I have to confess to being a tomato nerd. To me, tomatoes are the easiest to grow, the easiest to take care of, and you have such a great variety of sizes and flavors. And when I'm looking at my plants, I'm also always wondering about what's going on at the genetic level? What's going on inside the plant? What's making tomatoes red or yellow, tiny or giant? So, when I found out that researchers are working to map the genomes of 22 different varieties of nightshades, the family of plants which include tomatoes, potatoes, and eggplants,
well, I just had to know more. And the exciting news, at least to we nightshaders, is that they've located the genes that control the size of tomatoes and eggplants, and then use CRISPR gene editing to grow bigger fruits. I want to know more. Joining me to talk about his research and the current state of genetically modified crops is Dr. Michael Schatz, professor of computational biology and oncology at Johns Hopkins University in Baltimore, Maryland. Welcome to Science Friday.
Thank you very much. It's a great pleasure to be here today.
I've got to ask you first, how does a guy who's in the oncology department deal with tomatoes?
It's a great question. I would really say I would describe myself as a genome scientist. So, any sort of plant, animal, human, anything that has a genome I'm interested in. I got started in this work more than 20 years ago at a research institute called the Institute for Genomic Science, where I started in microbial genomics. And then, over the years, I've just been fascinated and had the privilege to work in many different systems.
Okay, so let's get right into it because can you give me an overview of the tomatoes genome? I mean, how does it compare to other fruits and vegetables?
Yeah, so the actual genome has been mapped out for more than a decade now. As genomes go, it's pretty well behaved. It's about a billion bases in size, whereas the human genome is about three billion bases in size. There's two copies of every chromosome. The plant world has great diversity there. The small genomes are much smaller, but the big genomes are much bigger. So famously, the wheat genome is about 18 gigabases, so many times larger than humans. So it's of kind of moderate size, bottom of complexity, which actually makes it a great system for doing genetics on. So that we can kind of really, you know, kind of handle all that complexity.
So we have fruits and vegetables that have a lot more chromosomes than we do.
That's right, that's right. Even our friend, the strawberry, has 12 copies of every chromosome. Sugar cane has between nine and 14 copies. So there's great complexity in there. And that's actually part of the connection to oncology. You know, that's one of the hallmarks of cancer where there's something called aneuploidy, where you make it extra copies of extra chromosomes. And there's some lessons that can be shared between the plant world and the human world and even in oncology.
Yeah, that's really interesting. So I understand that you began with mapping the genome of the African eggplant. And for those of us who are unfamiliar with that, can you give us an overview of what an African eggplant looks like?
As you said, you know, tomato is part of this larger family of nightshades. It includes eggplants and potatoes, but also in addition to kind of those major crops, there's hundreds of these more indigenous crops. So African eggplant is in this nightshade family. It's grown quite extensively in Central Africa. It's grown quite extensively in South America. It's becoming more popular in the United States. In fact, that markets like Trader Joe's, you might see it. It's sometimes marketed as a pumpkin on a stick because it has sort of a pumpkin-like shape, but it's actually an eggplant variety. So people are growing it. There's a lot of interest into it. The genome is pretty well behaved. It's sort of similar to tomato. It's a sort of a close relative in the same way that, I don't know, our friends, the chimps or the gorillas, are close relatives to the human genome.
Right, right. So you figured out? How the genes control growing these big eggplants? And how were you able to then use that to grow bigger tomatoes?
Yeah, so as I mentioned, the genome was mapped out more than 10 years ago. And there's been just a lot of research into some of the key genes and variants that modulate the size of fruits and tomato. But the opportunity is, well, there's all these other species, African eggplant and many others around the world, that have unique flavors, unique sizes, unique colors, tastes, but they're relatively small, they're hard to grow at a sort of at large scale. Maybe they're really sensitive to the environment. For any number of reasons, there's interest to kind of develop these other plants that are sometimes called indigenous crops, or sometimes just complete wild species. So we have some collaborators in Central Africa that have been growing African eggplant, and they were just really interested, like we all are, in what really is sort of modulating the size.
Why are some bigger? Why are some smaller? And the opportunity was to take genetic information that we already knew from tomato, and then try to use that to advance our understanding and advance the development of the African eggplant.
So did you actually cross a tomato with an eggplant? How did you actually use the genes from one to change the size of the tomato?
Yeah, they're a little bit too far apart to do crosses like that. But thanks to all the advances in sort of the genome engineering, we can kind of do a more directed editing, using that CRISPR-Cas9 technology, where if we thought there could be certain variants, certain sequences of DNA, we can now engineer that into this cousin. So specifically in tomato, there's a very classic gene called Clavata3 that has been known for many years as being important to the size of the fruits. In African eggplant, some are large and some are small. We did a genetic analysis of what variants are really important for modulating that size in African eggplants. We expected to see Clavata3 would be important, and we did find that that was important.
But along the way, we identified another enzyme, and it's still a little bit mysterious how it works, but we did identify another enzyme that seemed to be highly related to fruit size in African eggplant. And to validate it, we brought that mutations of sort of the related enzyme in tomato, and it turns out that also modulates fruit size in tomatoes. So there's this great exchange of information. From tomatoes into African eggplant and then right back to tomatoes. So it was all the whole sort of family, the whole nightshade system was sort of elevated through this research.
Uh huh. Well, what part of tomato actually gets bigger when you, when you modify it and you bring that trade in, which part of the tomato grows and how big can you get it to grow?
Yeah. You ever cut a tomato in half, it's sort of organized into these seed compartments. Those are called locules. The locule is a quantitative trait. The same way, you know, healthy people kind of have ten fingers and ten toes. You know, depending on the variety of tomatoes, sometimes there may just be one locule, there may be two. You know, a big beef steak will have, you know, many of these sort of large locules. So this clavata enzyme is really important for modulating the number of locules. The fruits that have more locules tend to be larger fruits. It's kind of that simple.
You know, but sometimes when you get these bigger varieties, they look pretty on the store shelf. When you eat them, they don't taste that good. I mean, could you, could you preserve that flavor in the tomato when you modify it?
That, that's one of the hopes we think about, you know, in the United States, the Heinz variety, the Heinz company. You know, it was a variety that has this interesting history from Central America to Europe and then back again to North America. You know, it, it's grown at massive scales, but like you mentioned, it'd be, it'd be exciting and a real opportunity to bring in some of these unique flavors from all over the world of all these different varieties. I've, I've had, I've had some nightshades that taste like a cross between a pineapple and a tomato and, and all these like exotic flavors that you just wouldn't encounter. And how fun and exciting it would be if those could be part of our diet as well.
Technically modifying these plants versus the traditional crossbreeding. You know, you, you can select for size and color and flavor with the traditional modes of plant breeding. And we see all shapes and sizes of tomatoes in the grocery store. So sell it to me. What's the benefit?
It's, it's a great question. And, you know, and of course that, that opportunity still exists and of course we still pursue it. But I would argue it's it's slow, it's limited. It sometimes will accidentally, while we're maybe targeting, you know, say, fruit size or the shape or whatnot, along the way, we may lose other important genes for disease resistance. Some of the flavor profiles may sort of accidentally get lost. But now, thanks to all these advances in the biotechnology, we have, you know, we have exquisite technology to sequence genomes, we have exquisite technology to modify them. Rather than kind of, you know, waiting for some random event to occur, now, you know, with laser-like precision, we can get in there and apply the edits very, very specifically. And we also have a lot of understanding of what they're doing.
So it's not that we're just, you know, poking around in the dark. We can do this in a very focused way to very rapidly advance on this. The modern tomatoes took hundreds of years to develop from the wild species, and now we can do it basically in one generation. So in one season, we can, you know, very rapidly advance on it.
When are we going to see these guys in the grocery store? And that must be the goal, right?
I mean, we're already seeing this, you know, you know, some of the more progressive grocery stores are, you know, are starting to accommodate consumer tastes. And, you know, I already mentioned that, you know, these so-called pumpkins on a stick are sometimes available, mostly as an ornamental. I think there's interest from consumers, there's interest from the producers, they just, the yield is low. It's just kind of that simple. So if we can sort of accelerate the yield, you know, through larger fruits, I think that will be a huge advance to make them more productive here in the United States. And I will say, you know, in other parts of the world, this is a major food crop. And if, you know, if there's any sort of food sensitivities, there's this immediate benefit to be able to sort of just develop larger fruits and just have more calories and just
sort of make sure there's food security around the world.
But speaking of other parts of the world, there's also a great pushback to genetically-modified organisms, right? Genetically-modified food, which this is. I mean, is that, has that pushback gotten less over the years? Is it going away, or is it still there?
I think it's still there. I think some people are very progressive and are very interested in sort of the opportunity to, you know, bring in new flavors, bring in advances on size or disease resistance. But I do think that, you know, there are others that are still have some concerns. And, you know, as a person, also as a father, you know, I'm worried about the security of my foods for my children. You know, that'd be the last thing I'd want to do is give them something that was dangerous. But I think that's, you know, another thing to realize about these technologies is, again, because we have so much control and laser-like precision to introduce these edits, we can do it incredibly safely. I should comment, you know, the varieties that we've done today are not commercially available as a food product. This was a research product. But our goal here is to
work with some of the breeders, you know, and help them advance on this so that it could be available as a food crop.
We have to take a quick break, but don't go away. More on this when we come back.
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Now, if you can find the genes that control the size of the nightshades, the eggplants, the tomatoes, can you find the genes that control the flavors of them also?
In addition to fruit size, we're interested in a variety of other traits. One that's really important is called flowering time. And that really is important as you take crops to different parts of the world, where sometimes the days could be longer or shorter, just depending on where the sun is. That's a really important crop for making it productive. And then, like you suggested, we're also very interested in some of the flavors. A few years ago, we did a study in tomatoes, and we could find out some of the genes and some of the variants that were associated with the flavor profiles. So absolutely, we're very interested in the genetic basis of that as well.
You know, I have a catalog of nothing but tomato seeds.
Yes.
Tomato plants, right? You may be familiar with it yourself. And there are so many different colors and varieties. I mean, and last year, home gardeners were really excited about about a genetically modified purple tomatoes. I mean, photos of it look almost unbelievable by how purple it is. It was crossed with a purple Snapdragon plant. Could you? Could we see the demand for these kinds of specialty fun plants increasing?
Absolutely. Yeah, there's been some great work on these purple tomatoes. You know, they were kind of developed through crosses and they have some interesting kind of antioxidant capabilities there. My understanding is when that became sort of commercially available, you know, basically sold out in one day. There's just such huge demand to grow these unique varieties. And people are just really excited about it. Another great example is there's another sort of ornamental plant, the petunia. And then there is a commercially available called the Firefly Petunia that glows in the dark. And it's just really fun to have, you know, it's just amazing to think about what's possible today and then even more so in the future as we get sort of even better at doing the editing, better at predicting and understanding which variants are associated with which traits.
Could you get a tomato to glow in the dark?
I bet we could. I bet we could. We haven't tried it yet, but I bet we could.
In case you're just joining us, I'm talking with Dr. Michael Schatz, professor of computational biology and oncology at Johns Hopkins University about his work using gene editing to grow bigger tomatoes and eggplants. This is Science Friday from WNYC Studios. Now, you've been doing this a long time, as you've said. You must have watched the technology improve to genetically modify crops. Tell us how, what you've seen here.
Yeah, absolutely. So, you know, as I said, I've been in genomics now about 25 years. And it's, we've basically emerged from the, I don't know, the Stone Age into the Space Age. One of the first projects I worked on about 20 years ago was we were looking at, in Hawaii, there's a variety of apaya that was really susceptible. To a virus that was being passed around is something called the papaya ring spot. And it was basically killing off the industry in Hawaii. So there was an early effort there to do genetic engineering to make it resistant to this virus. But the technology available, you know, this predates the, you know, kind of the identification, the discovery of CRISPR. So there was a very sort of classic way of doing this using something called a gene gun.
Where small particles of gold would basically pierce through the cell membrane. That would allow for bacteria to kind of sneak inside of, inside of the cells. And then in a very random way, that would sort of induce of small fragments of DNA to be incorporated into the genome. It takes a lot of, I don't know, artisanal work to make that gene technology effective. But to their credit, the researchers were able to develop that transgenic variety, this son up a variety of papaya. They basically saved the industry in Hawaii. That was the early days, you know, it was a very random, very sort of stone tool approach. But like I said, now it's space age where, you know, with laser like precision, we can specifically identify out of the billions of bases that are there.
We can say, yes, this A has to be changed to a C or a T or whatever we need it to be. To manifest the trait that we're interested in.
Right. All right. Well, the final question to you, I actually am coming full circle because I began the interview talking about. Your work as an oncology and cancers. You also work with the human genome there. What is the most exciting application of genomic sequencing you're working on right now?
It's many. So as I mentioned, you know, our ability to sequence genomes has advanced enormously over the last few decades. I was part of something called the telomere to telomere consortium. Where a couple of years ago, we put forth the first complete picture of a complete human genome. And that was out of sort of a reference sample, but what's to be exciting to me is now we can apply this to patient samples. So Johns Hopkins, I have a collaboration with Winston Timp and Ellison Klein. Ellison is a world's expert in pancreatic cancer and especially familial cancers where it runs in the family. Where, you know, a patient will have pancreatic cancers, but then their brothers and sisters or their parents, aunts and uncles, grandparents. You know, it just runs through the family. So so that it looks like there's a genetic component to this.
So Ellison has been for many years trying to identify the specific genes and variants that are associated with that familial cancers. But collectively, that only explains a few percent of all the cases. So we're really excited to take these technologies to read off complete genomes. And if we could read off the complete genome, there's just no place left for these mutations to hide. And then the hope is potentially using CRISPR or other technologies, we can introduce some sort of therapeutic that will prevent the cancer from forming in the first place. So I'm really excited about the possibilities to advance on human health in addition to our food security.
Wow, that's quite the range that you're studying there. From tomatoes to cancer. I'd like to thank you for your work, Dr. Schatz, and for taking time to be with us today.
Thank you so much. It's been a pleasure.
Dr. Michael Schatz, Professor of Computational Biology and Oncology at Johns Hopkins University, based in Baltimore. That's about all the time we have for now. A lot of people helped make this show happen. John Dancoski.
Annie Nero.
Jason Rosenberg.
Rasha Urdi.
I'm Ira Flatow. Thanks for listening.
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