Is There A Method To Plant Mutation?

IRA FLATOW: This is Science Friday. I’m Ira Flatow. When you learned about evolution in school, the explanation likely sounded something like this. DNA mutates randomly. Some of those mutations make an organism more likely to survive and have offspring with the same mutation. Other mutations might make the organism less likely to survive, so it dies out. So natural selection ensures that only the beneficial mutations end up carried on in a population.

But researchers are increasingly questioning that first premise and asking if mutation really is random. Or is the relationship between natural selection and mutation more complicated? You’ll see what I mean here, because new research appearing in the journal Nature this week takes a closer look at mutation in plants. And as the team writes, their results suggests that the genome might not randomly mutate, but protect itself from mutations in some of the most crucial locations.

Here to explain– I’m sure better than I can– is Dr. Grey Monroe, lead author on the new research and an assistant professor of plant genomics at the University of California Davis. Welcome to the show.

GREY MONROE: Thank you so much for having me, Ira.

IRA FLATOW: Did I get basically that thumbnail correct?

GREY MONROE: That was excellent. I’m impressed. That was a very good thumbnail.

IRA FLATOW: I’ll thank my eighth grade Mrs. Pfeffer for science, teaching me that.

GREY MONROE: Perfect.

IRA FLATOW: And the big premise is that mutation is random, right? But that organisms adapt because the bad mutations don’t survive. The good ones do. So why are researchers like you starting to question that?

GREY MONROE: That’s right. So thinking back all the way to our high school biology, we were told that mutations are random. And so this is something that, even as a practicing geneticist and evolutionary biologist, I never really questioned until we were looking at some data that suggested something very different. So we have been looking at mutations in a plant called Arabidopsis. It’s a little sidewalk weed. It’s something that you could hold in your hand. It’s a small little plant, and it makes for an excellent model system that we use in the lab to study mutation.

And so what we’ve been doing is sequencing the genomes of many individuals of this plant with experiments we call mutation accumulation experiments. And when we look at the distribution of these mutations across the genome, what we’re finding is a pattern that’s definitely not random. So there are some places in the genome that seem to be protected from mutation more than others. And when we asked what kind of regions of the genome are those, what we discovered is that those are the regions of the genome that are most important for the biology of this plant.

IRA FLATOW: And what regions were protected more than others?

GREY MONROE: So when we look at a genome, it’s made up of a lot of different parts. So some of the places in the genome are those responsible for coding for proteins. And proteins are, of course, the building blocks of all cells and organisms. And we found that the regions of the genome that code for genes have a much lower mutation rate than the non-gene regions of the genome, which we think of as less biologically important because they don’t code for proteins. So we found that genes that code for proteins have lower mutation rates.

And then when we compared genes what we found is that genes that have the most essential biological functions have the lowest mutation rates among genes. And so what this suggests is that the places in the genome that are most vulnerable to mutation, the places where mutations would most likely have harm, are the ones that are most protected from mutation. And so this is a very different idea of random mutation that we traditionally think of in evolutionary biology.

IRA FLATOW: Well, would you think that this is something that the plant evolved to do to protect itself?

GREY MONROE: That’s exactly right. So what we think is that this is a strategy that has evolved, that this plant and other organisms likely have developed complex molecular machines to repair DNA and that these DNA repair genes are possibly targeting certain regions of the genome in preferential ways.

IRA FLATOW: Yeah, is there a metaphor that you can compare this to the way we normally live?

GREY MONROE: There is. So I like to think about the metaphor of the DNA in your genome representing the blueprint for a car, for example. The parts of the car are the proteins that make up a cell. And so if we think about a car, some parts are more important than others.

So for example, the shape of the wheel is obviously a very important feature of all cars. All cars need to have round wheels. And so whatever part of the blueprint tells the manufacturer to make their wheels round is a very important part of the blueprint, whereas part of the blueprint that tells the manufacturer what color to make the car is possibly a less important feature.

And so if we imagine having imperfect copying machines, and so this is analogous to DNA being damaged during replication, for example, we would need to go and check the copies of the blueprint to make sure there’s no errors. And this is analogous to DNA repair. And you might imagine that it would be advantageous to double-check the portions of the blueprint that encode for or provide the plans for the most important features of the car. So it would be very important to double-check that the page that tells the manufacturer to make the wheels round would be something that you would definitely want to make sure is correct, whereas something less important, like the color, can be allowed to change in ways that are not as harmful and possibly even beneficial.

IRA FLATOW: So does the plant have a mechanism, then, for making sure, for double-checking that the wheels are still the same?

GREY MONROE: That’s a great question. So the mechanism that we think is going on– and this is largely supported by some excellent work that’s been done in the realm of cancer genomics. So obviously, for cancer, understanding why mutations happen more often than not in different places of the genome is very important, with interesting, important implications for human health. And so what they’ve shown, and what we have found evidence that supports, is that the structure of how DNA is actually organized inside of the cell is what governs where mutations are more or less likely to occur.

So if you were able to zoom in inside of a cell, what you would find is that inside of the nucleus, the DNA is actually not just sort of haphazardly a tangle of DNA molecules. It’s actually organized. And it’s structured as coils around proteins called histones. And so these histones provide kind of the backbone for DNA inside of cells.

And these histones can actually be modified with certain chemical marks. And what we found is that these chemical marks are not distributed randomly across the genome. There are certain chemical marks that are found much more often and almost exclusively inside of genes, inside of those regions that code for proteins. And these chemical marks are also more often found in these essential genes.

So if we think, going back to the car metaphor, these marks are more likely found in the regions of the genome that code for these essential parts, like the wheel in the car metaphor. So if we think about it, it’s kind of like if the blueprint was highlighted in certain places. If the wheel blueprint page had a highlight mark on it, this is essentially what’s happening. And what we think is going on is that these chemical marks on the histones are providing the signal that’s allowing DNA repair to go and preferentially fix mutations that otherwise would occur in these important regions of the genome.

IRA FLATOW: This leads me to ask that if the plant is going through mutations, wouldn’t it have to mutate in the area it needs to mutate to protect itself, to create these chemical markers? Didn’t it initially have to mutate to protect itself from mutation?

GREY MONROE: That’s a great point. So this very process, all of these features, this complex machinery, had to arise at some point by mutation, which is kind of interesting because it gives rise to this kind of circularity in the evolutionary process that we might not have anticipated before, where you have mutations that give rise to mechanisms that change what kind of mutations happen. And so some might find this circularity troubling or problematic, but I actually tend to view it as rather beautiful and an interesting new wrinkle into our understanding of how evolution works.

IRA FLATOW: So what happens to plants physically when these essential genes aren’t correct, they aren’t repaired?

GREY MONROE: So in plants, just as in humans, when essential genes are damaged by a mutation that disrupts its function, we see disease or even death, or basically very harmful traits. So we see plants that just look really bad, basically.

IRA FLATOW: What about the opposite? Where is the most mutation happening in this plant?

GREY MONROE: Right. So we found that these essential genes have low mutation rates, but when we also asked, what genes have the highest mutation rates, these results were also really interesting. We found that genes that are involved in plant adaptation and interaction with the environment are the ones with the highest mutation rates.

And so our lab is also quite interested in understanding how plants adapt to climate. So this leads to some very interesting questions about, what is the role of this increase in mutation rate in these environmental response genes? Has this facilitated more rapid adaptation to climate? And when we think about climate adaptation, where environments are changing very rapidly, the introduction of new mutations in these genes could facilitate more quick adaptation than we would have otherwise expected, which is something that we haven’t really thought about before, but now we’re currently working on.

IRA FLATOW: So if they can’t flee the changing climate, they adapt to it.

GREY MONROE: That’s exactly right.

IRA FLATOW: You mentioned that this plant you’re studying is a weed. If I remember correctly, it’s something like a mustard plant, something like that?

GREY MONROE: That’s right. It’s in the mustard family. So you can even eat it. You can eat it in a salad if you want. It might be a little spicy.

But yeah, it’s in the mustards, and it’s been one of the most well-studied model systems in plant research and genetics for quite a while. So imagine it’s kind of like the way we think about the fruit fly as a model system for animal genetics, or a lab rat. This is the lab rat of plants, basically. But it also grows in nature.

IRA FLATOW: Yeah, and it does very well in nature, right? Could the higher mutation rate in that part of the genome be related to that?

GREY MONROE: That’s right. It’s been successful across much of the world. We can find it in Europe, Africa, North America, and it’s spread. And one question is, has this interesting pattern of mutation bias– has this played some role in helping it adapt to new environments in a way that it wouldn’t have otherwise? So this is something we’re quite interested in.

IRA FLATOW: Yeah. So how does this research upset our entire theory of evolution? Does my eighth grade teacher have to change something?

GREY MONROE: You know, I don’t think that it upsets our entire theory of evolution, because we actually think that these very processes are themselves the product of natural selection, that they evolved because they provide this benefit. I think that it adds an interesting wrinkle to the evolutionary story. I think that it means we’re going to have to say something more complicated about mutation when we teach students. I think saying, mutations are random, and sort of period, end of story, is an overly simplified way of thinking about mutation. And a model and theory of evolution that includes these non-random mutational processes, I think, is a very interesting and elegant new way of understanding evolution with new dimensions.

IRA FLATOW: You know, I remember when one of the big surprises of the Human Genome Project was finding these huge regions of the genome that we used to call junk DNA, or silent– they didn’t seem to code for anything, and now we discovered that there was some use for them. Is there anything about this mutation bias that might help us get closer to understanding that particular mystery?

GREY MONROE: That’s an interesting question. So in this sense, what we’re finding is that this area of the genome that may have been thought of as junk DNA at some point– these regions that don’t code for proteins, for example– that these have an elevated mutation rate. And one interesting implication of this, or one interesting question that arises from this, is, does that increase in mutation rate in this so-called junk DNA mean that this type of region of the genome is contributing more to adaptation, because it is a place where there’s novel genetic variation being generated more often? So I think it definitely adds an interesting element to that idea.

IRA FLATOW: Well, you give the genome more flexibility if you give it a place where it can mutate.

GREY MONROE: Exactly. I mean, mutations are the ultimate source of all genetic variation. It’s necessary for adaptation and evolution. So there has to be mutation, otherwise organisms couldn’t evolve. So there needs to be somewhere where mutations are allowed to happen, we might think of it. And if not, then there wouldn’t be evolution, so where those places are that mutate more often might be hot spots for adaptation.

IRA FLATOW: This is Science Friday from WNYC Studios. In case you just joined us, we’re talking to Dr. Grey Monroe about evidence that in evolution, mutation may not be random. Now, I know you’re a plant researcher. You spend a lot of time there in the laboratory with plants. But you must be thinking about it, when you’re having a beer with your colleagues, about whether the same thing is going on in animals.

GREY MONROE: Absolutely.

IRA FLATOW: Right? Where DNA mutates less in more important regions, and vice versa?

GREY MONROE: Absolutely, of course. You can’t help but think, is this something that’s going on inside of our own bodies? And you know, I’m not a human geneticist, but I’ve been really excited to see what’s going on in some of the work, especially in the realm of cancer genomics, and looking at the discoveries that are being made about where mutations happen in human cells. And what we find is that there’s actually similar patterns. So there’s been a lot of really exciting work that’s come out recently that shows that mutation rates can also be lower inside of genes in humans as well. And this obviously has interesting implications for human health and cancer.

However, I want to point out that I think– we actually hypothesize that there’s probably differences between humans and plants as well. And this is because, if we go back to this idea of these histones that the DNA are wrapped around, we know that animals and plants have a different sort of language of how these histones are modified by chemical marks. And because the histone chemical mark language is different between animals and plants, we suspect that the underlying mechanisms that explain why they both might have these interesting mutation biases might actually be slightly different.

IRA FLATOW: We talked a little bit about how plants may be adapting to climate change. And I know you spend a lot of time researching how plants, especially crops, might be better adapted to drought conditions. Especially farmers will have to feed people in the face of climate change, more extreme weather, and so on. If this is how evolution is actually working, what practically might change about research like yours?

GREY MONROE: Yeah, we’re quite interested in how we can also generate crops that are adapted for new and changing and stressful climates for plants. And one of the ways to do this is with breeding. So breeding is basically an applied science of evolution and genetics, where we use the principles of evolution and genetics to improve crops that we want to have higher nutrition or better stress tolerance.

And so because essentially breeding is a genetic and evolutionary science, it relies on an accurate theory of evolution and genetics for it to be effective. And so this means that if we’re assuming that mutations are random, if this is a core assumption of our theory, then we might not be doing as good a job as we could be otherwise. So it could obscure our ability to discover genes that are useful for accelerated breeding. And it could even mean that there are limitations to the type of genetic variation that are available for breeding that we otherwise wouldn’t be aware of. And so having a sense of the extent of this mutation bias in crop species is also really important for developing better breeding systems, we think

IRA FLATOW: I think that’s a good place to end it right there. I’m afraid we have to make like a plant and leave it there.

GREY MONROE: [CHUCKLES]

IRA FLATOW: We’ve heard so many bad plant dad jokes, I’m sure. Thank you so much, Dr. Monroe, for joining us.

GREY MONROE: Thank you so much for having me.

IRA FLATOW: Dr. Grey Monroe, assistant professor of plant genomics at the University of California in Davis.

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