LIFE
AND OTHER STORIES
Maria Logacheva
Running from a Bear
LIFE
AND OTHER STORIES
Maria Logacheva
Running from a Bear
  • Story
    on plant genetics – how their genome differs from ours, what ideal buckwheat looks like, and why genetic editing holds more promise in agriculture than in medicine
  • Story told by
    Maria Logacheva, Assistant Professor at the Skoltech Center for Molecular and Cellular Biology, an expert in plant genetics
  • Story asked by
    Agata Korovina, Science journalist
  • Story recorded
    in December 2021
— You specialize in plant genetics. Could you explain what makes them special after all?
— Many plants have incredibly large genomes. The human genome is roughly 3 billion nucleotides in size. In plants, it's typically five times larger. The record is 150 billion nucleotides, which is 50 times bigger than the human genome.
And honestly, there is nothing beneficial about such a large genome. It contains numerous elements that could have been easily omitted. Mostly, such a large genome size comes from the so-called mobile genetic elements that are akin to viruses, meaning they are remnants of a viral attack experienced by these organisms' distant ancestors.
Mobile elements exist semi-autonomously. They reside in the genome and can be activated to produce proteins and their own genetic copies, which will also be integrated into the genome later on. But generally speaking, the organism doesn't need them.

— So it's essentially residual information.
— Essentially, yes. However, some mobile elements can prove beneficial to humans. If a mobile element embeds itself in a gene, the gene will be destroyed, and the plant will mutate. Some of these mutants are useful to breeders. For instance, a plant has fruit that falls off, which is bad for us as it hinders efficient harvesting. If you disrupt the gene responsible for fruit shedding, the fruit will naturally stop falling. While this isn't beneficial for the plant, it's advantageous for those who wish to consume the plant's fruit.

— Are mobile genetic elements the sole reason why plants have such enormous genomes?
— There is another reason. Besides mobile elements, plants have a penchant for doubling their DNA, a process known as whole genome duplication. When this happens in animals, the consequences are catastrophic. A human, mouse, or any other mammal with such a duplication will likely die before birth in the prenatal period, and if it is born, it will lead a short and tragic life. When a person has just one extra 21st chromosome, they are diagnosed with Down syndrome. And here we have whole genome duplication, where each chromosome doubles. However, plants with whole genome duplication actually become more resilient and can adapt better to environmental conditions. For example, one of the five most common plants on Earth is shepherd's purse. It can be found on all continents and in nearly all climate zones, something it achieved through whole genome duplication.
Photographer: Evgeny Gurko /
for “Life and Other Stories”
— Can the number of genes decrease instead?
— Yes. This process is known as reductive evolution. This is prevalent in both plant and animal parasites. Parasites are entirely or partially dependent on their host during certain life stages, so they can safely discard fragments of genetic networks needed by free-living organisms. This gives parasites a selective advantage as they don't need to expend resources on replicating extra DNA, expressing genes, or producing proteins. They essentially shed unnecessary junk and can reproduce faster as a result.
Here is another example. When people think of plants, they usually envision something green. Green means chlorophyll, and chlorophyll means photosynthesis. For us, a plant and photosynthesis are practically synonymous. However, there are plants, about 1–3% of them, that have abandoned photosynthesis. They survive either by parasitizing other plants, attaching to them, infiltrating their conducting system and essentially siphoning off nutrients, or through symbiosis with fungi. And they lack all those numerous genes that produce the proteins required for photosynthesis.
Thanks to this ability, they can inhabit areas that are completely inaccessible to regular photosynthetic plants due to darkness. But it's clear that this is a dead-end path because once you discard such a complex trait, you can't get it back. So it's a one-way ticket.

— You're studying the buckwheat genome. What are you trying to discover? And how will that information benefit us in the future?
— Firstly, it's very complex. I'd prefer not to focus on it for so long, but in a sense, it's unavoidable. For instance, all scientists working on plant genetics have a model object — Arabidopsis thaliana. Its genome was published over 20 years ago, but it's regularly being updated. The tenth version of this genome has now been published. Minor errors or inaccuracies are constantly being found. And this happens with the genomes of all plants. It's impossible to perfectly assemble any genome all at once.
By plant standards, the buckwheat genome isn't very large, but it contains many mobile elements. They're recent, which means they're very similar to each other. And this poses problems for the programs that assemble the genome.
Why is assembling a genome so challenging in the first place? If we only had a unique sequence, a piece that appears once in the genome, it would be much simpler. But there is no such thing as simple in nature. Instead, there are many sequences that look identical, but they are located in different parts of the genome. The assembler tries to piece these fragments together like a puzzle and repeatedly comes to a halt. Imagine your puzzle has many identical pieces. Suppose you're assembling a sky with clouds, and these clouds are identical. And you don't know which pieces to connect.
When the assembler encounters these "clouds", it must either break the assembly — which would be fair, because we can't be sure that this "cloud" should be in this corner of the "sky" and not that one — or it can continue the assembly, but then we risk creating many erroneous connections. Secondly, we're studying the buckwheat genome because buckwheat is fascinating in terms of its position in the system of flowering plants. It's distinct from other crops that are extensively studied, primarily cereals such as wheat, rye, corn, and barley. All these grains are closely related. And when we learn something about one crop, we automatically apply this knowledge to its relatives. But buckwheat is far removed and not closely related to any well-studied crops.
Thirdly, we're studying the buckwheat genome because it's a crucial crop for our country. You may have noticed this. When COVID-19 hit, everyone immediately rushed to buy buckwheat.

— And the better we understand buckwheat's structure, the more effectively we can enhance it, right?
— Right. Because while we're actively engaged in buckwheat breeding, it's not based on modern molecular methods. This results in a longer and less predictable process. And the reason we don't use modern methods is because, in truth, our knowledge about buckwheat is quite limited.
In such circumstances, the only viable option is to crossbreed plants, observe their progeny, assess the state of the trait we're interested in, and proceed from there. However, if we understood the molecular foundation of buckwheat, we could predict the plant's characteristics at a much earlier stage.

— Can you describe the ideal buckwheat, buckwheat of our dreams ?
— To start with, buckwheat is not like wheat, which has a single compact ear where flowers bloom more or less simultaneously and seeds develop at the same time.
Buckwheat is a tall plant with many branches. Its flowering period is quite long, which results in the seeds ripening unevenly. No matter when you choose to harvest it, you'll likely gather about five percent of the crop, not more. Additionally, buckwheat is cross- and insect-pollinated. On one hand, this is beneficial as it produces honey. On the other hand, it makes us reliant on the whims of weather and bees — a dependency we'd rather avoid. Therefore, the ideal buckwheat should be self-pollinating, sturdy, compact, not too tall, and have seeds that ripen uniformly.
Currently, active work is being done in this direction. We are collaborating with a group of breeders from the Federal Scientific Center of Legumes and Groat Crops, and I'm hopeful that this will yield practical results.es that code for proteins. This speaks volumes.
Photographer: Evgeny Gurko /
for “Life and Other Stories”
— You mentioned plants that don't rely on photosynthesis. Could we enhance the buckwheat genome to make it possible to cultivate it in a basement, for example?
— Being a plant that doesn't photosynthesize isn't really advantageous. On one hand, it's beneficial as you don't need light. On the other hand, you still need energy. Most plants get their energy from light, while non-photosynthesizing plants get it from other plants or fungi. So we would need another plant, or fungi, or some other external energy source.
Moreover, most non-photosynthesizing plants are small because it's not possible to accumulate a large biomass through parasitism. They produce many seeds, but those are tiny and dust-like.

— What is the most important thing that has happened in your field in recent years?
— The decoding of the human genome, but it's important for a very specific reason. Previously, the idea was that if you have a species that interests you — say, Drosophila, Arabidopsis, or humans, — obtaining a genome sequence for it would be a major achievement. In 2003, the human genome was published, and one of the most unexpected findings was that, essentially, it didn't allow us to draw the conclusions we wanted to. It's merely a reference point to which we need to add knowledge about gene activity (expression profile) in different tissues, organs, and at different stages of development, as well as knowledge about diversity — because even minor differences are very important.
The genome was sequenced by white Europeans and for white Europeans, but there are many other people living on the planet besides them. Human genomes can vary in terms of the number of genes, their composition, and regulatory details.
All of this is currently being actively studied. In other words, scientists are striving to expand their sample pool within a single species. The global trend is to build upon existing knowledge.
Photographer: Timur Sabirov /
for “Life and Other Stories”
— Is this trend also evident at the intersection of molecular biology and botany?
— Yes. In the past, identifying the sequence of an interesting species and publishing a paper in Nature was considered an achievement. Now, scientists are trying to select groups that contrast in some characteristics. For instance, when it comes to cultivated grains, many of them differ in their flowering times. Some, known as winter crops, require a period of cold weather. They survive the winter and then sprout and bloom. And some can be sown in the spring and will grow and bloom normally. To better understand how this is controlled, we need to compare these two contrasting groups.
If we only consider one of them, we likely won't understand anything unless we get incredibly lucky and have one of our hypotheses confirmed. If not, then we need to study more species that differ in the trait we're interested in. For example, some species can withstand extreme stress conditions, like high levels of soil salinity, while others cannot. By comparing them, we can understand why those that can tolerate extreme conditions are able to do so and which genes and gene activity are to thank for it. This knowledge can then be transferred to other species through genetic modification.
This is a rather complex and lengthy process because there are about 300,000 species of plants, each with its own unique characteristics. They differ from each other much more than, say, a human differs from a mouse. And what works for one species may not necessarily work for another. In fact, it probably won't work because many plants have their own unique reproductive features, inflorescence structures, and regenerative abilities.
— So, the overall global trend at the intersection of molecular biology and botany is to compare different plant species, right?
— Yes. And also personalization.
There is a concept known as the pangenome. Scientists used to think that defining the genome was all they needed. Now, they're saying that there is not only the genome but also the transcriptome, which shows the level of gene activity. Some genes are active throughout life, while others are activated only at specific times and initiate processes needed during those periods. For example, when the day length increases, something triggers a switch, and genes that lead to the plant blooming are activated. To understand how this happens, we need a detailed map of gene activity during different stages of life in different organs of the organism. In addition, within each species, there is a great diversity in genome structure.
Creating a complete, detailed picture by comparing the genomes of different organisms is what is referred to as pangenomics.
This is currently the prevailing concept, and it permeates all fields of science. Pangenomes are being constructed for bacteria, barley, and wheat. Naturally, there is also a lot of work being done on animals.

— Which works by your Russian and foreign colleagues are worth paying attention to in your opinion?
— When it comes to genomics, especially pangenomics, it's all about large-scale efforts. There are big consortia working in this field, and the contributions of individual authors may not be as discernible. But I would highlight the work of my colleagues in Pavel Pevzner's lab. He and his team have developed a genomic assembler, SPAdes, which they continue to improve and adapt to new technologies. Many important works on obtaining new genomic sequences, pangenomic comparison, comparing many genomes within a single species, technical refinement, and improving existing reference sequences were either written with his help or authored by his students and colleagues.

— If we fast forward a few decades, what could humanity achieve with molecular biology in medicine?
— The obvious answer, which everyone gives and I can't avoid either, is that genomic editing will be widely used. This potentially allows us to do things that seemed unbelievable until recently, like treating hereditary diseases. In other words, we could edit a nucleotide that causes an unfavorable condition and create a normal version of the gene. But that's all theory. Sadly, there are currently many obstacles to the therapeutic application of this technology in people.
Firstly, it's difficult to deliver the editing system inside a specific cell. The system is composed of a protein and RNA. The protein slices the DNA, and the RNA essentially guides the protein to the precise location of the DNA that needs to be cut. While this may sound straightforward, for this system to function, it must be delivered into the nucleus. And the nucleus is located inside the cell. When we consider a person who has already been born, it's clear that we can't modify all of their cells.
The second issue has to do with accuracy. There is a risk of unintended changes occurring, not just the ones we aim to make. This could lead to a situation where "the remedy is worse than the disease". Although improvements will undoubtedly be made over time, I'd like to wish my colleagues working on this good luck. I'm confident that they will be able to advance this technology. However, I believe that such a procedure will be used only by people who have no better alternatives. areas tend to have significantly fewer allergies than their urban counterparts.
— With plants, however, it's a simpler process. What is the potential of these technologies in the field of agriculture?
— The situation with plants is much better. There will certainly be no objections from the ethics committee, and you won't be imprisoned by the government for your experiments. Generally speaking, we aren't overly concerned about the possibility of something bad happening to plants. And if we inadvertently affect other traits while searching for the desired one, it won't be as critical as it would be in humans.
Therefore, yes, this technology holds great potential. And there is a high likelihood that it will be well-received by society. It's no secret that many people tend to dislike GMOs. Regardless of how often we assure them that it's safe, people are uncomfortable with the idea of foreign genes being inserted into the genome of familiar crops like buckwheat, wheat, or others.
The new technology doesn't require the addition of any artificial constructs or genes from viruses or bacteria. It only involves making changes similar to those that naturally occur through evolution. People may perceive genetic editing as a more natural course of things.
The scope of what can be altered is quite extensive. But the simplest action we can take is to deactivate a gene, for instance, the one responsible for seed shattering. In certain cases, we can do the opposite and activate a gene, enhancing its level of expression and activity. This method even allows us to make plants resistant to antibiotics without introducing any bulky foreign constructs.
The only drawback is that it's technically challenging. We will be focusing merely on developing a protocol for this type of editing over the next two years. This is stage one. We will establish a methodology that allows other scientists to work with the genes they are interested in. In other words, our current objective is not to create a specific product that would increase yield but rather to demonstrate how such a product could be created.

— You mentioned how the genome is filled with unnecessary parts, errors, and so on. Some people compare evolution to a drunken plumber — as long as the system doesn't fall apart, it's all good. Does that mean they're actually right?
— Do you mean the fact that many of the structures and functional mechanisms that arise through evolution are less than optimal? If so, then yes. That's absolutely true. It's like in the joke about two people running from a bear, where the goal isn't to outrun the bear but to outrun your friend. In terms of evolution, to be successful is not to be the most successful, but to be to be better than your competitors. And that's exactly what happens.
This interview was first published on Biomolecule website on May 24, 2022
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