Scrambled DNA fragments could open doors to higher crop yields, new herbicides


I was cutting my grass when the battery in my iPod died. Instead of enjoying the distraction of music, my brain switched to its usual nerd mode of thinking about molecules. Within a few passes of cut grass, I was pondering the biggest “Why not?” of my scientific career: Could we discover new drugs and useful agricultural compounds by challenging organisms with clusters of random chemistry?

My background is in molecular biology – the study of DNA, genes and how an organism’s blueprints are decoded and assembled into life. The discipline requires an understanding of how molecular codes are deciphered and turned into functional biology. Anyone in this field is plagued with dreams of dancing molecules, interacting and performing the roles that turn DNA information into our food, the plants in our environment and our families.

Every day in the lab we move genes around. It’s easy. Not meant to generate new products for consumers, moving DNA is used as a research tool that lets us understand how specific genes work. A classic example is the NPR1 gene from the model plant Arabidopsis; it’s a defense gene that confers enhanced tolerance to disease when you drop it into almost any plant’s genome. Manipulating genetic information – in plants, microbes and some animals – is commonplace.

On that half-cut lawn it occurred to me – instead of inserting DNA information we understand, what if we introduced a scrambled mess of random DNA code into a plant or bacterium? Could we identify random bits of genetic information that could give rise to small proteins (called peptides) that change an organism’s physiology or development?

In all living things, the ‘words’ in the genetic material code for particular amino acids, so the organism can build the proteins it needs. Image: Boumphreyfr, CC BY-SA

Normally DNA encodes instructions that coordinate the order of the amino acid building blocks in a protein. Each amino acid has specific chemical characteristics. Strung together in a peptide chain, they fold into a protein that provides cellular structure or function, based on the complementary chemistries of its amino acid components.

My hypothesis was that a short, scrambled DNA message could give rise to a novel string of amino acids. This would be a small cluster of discrete chemistry that likely never existed before on the planet. The vast majority of the time it would be meaningless and just become cellular rubbish. But maybe on rare occasion it could do something new and desirable.

To test the hypothesis, our research team used randomized templates to synthesize trillions of random DNA fragments using simple DNA amplification techniques. Each was flanked by the genetic instructions to start and stop production of a peptide inside the plant.

Then we used standard genetic engineering techniques to insert a novel DNA sequence into thousands of individual Arabidopsis thaliana plants – and sat back to watch what would happen when the plants turned the random genetic information into little random peptides. We were hoping for cases where specific protein structures might find a connection with biological chemistry and we’d see the result in the plants themselves.

As the plants grew, we were blown away by what we observed.

In some cases, adding a random ‘gene’ had a big effect on how plants grew… or not. Image: Kevin Folta, CC BY-ND

Some plants were flowering early. Others were small and stunted. Others grew larger leaves. Some were loaded with healthy purple pigments. Still others grew up to a point…then died.

We then retrieved the particular random DNA sequence we’d added to each, a simple feat for a molecular biologist, and inserted the same sequence into new plants. Most of the time the random information affected the new generation of plants in exactly the same way, demonstrating that something was indeed happening related to the added, garbled information. We published our results in the journal Plant Physiology.

Related article:  GMO 'Right to Know' movement takes food off of plates of hungry in Africa, Asia
Follow the latest news and policy debates on agricultural biotech and biomedicine? Subscribe to our newsletter.

What is this random information doing inside the cell? The small random molecules generated from the inserted DNA instructions could affect a specific process, just by chance. They could bind a needed nutrient. They might inhibit a key enzyme. They could turn on flowering or protect a plant from freezing. Nobody really knows exactly how until the plants are examined in detail one by one. These new proteins may also be good models to design new useful molecules with similar chemical properties, but that are more durable in the cell. Our goal is to produce a compound that may be applied to crops to change the way plants grow and behave, or perhaps stop the growth of invasive or weedy plants.

The process is like throwing monkey wrenches into a complicated machine. Most of the time they clank around and affect nothing; but once in a long while a wrench catches in some critical gears and brings the machine to a halt. Other times the wrench might short-circuit a wasteful process, allowing the machine to run more efficiently. These peptides are molecular monkey wrenches.

Small proteins created through this process might be the future of safe, sustainable and specific weed control. Image: KegRiver, CC BY-NC-ND

Some of these peptides must interfere with an important biological process because they kill the plant. These findings bring to light new vulnerabilities in plants that researchers could exploit to develop environmentally friendly and nontoxic herbicides. Agriculture currently relies on a few relatively old chemistries, cultivation (using fossil fuels) or human labor to control the weeds that compete with food plants for resources. Good weed control means that valuable fertilizers, water and sunlight go only to the desired plants, rather than weeds. So new herbicide chemistries would be extremely valuable as farmers work to produce food for growing populations.

But why stop at plants? We are using the same approach to discover the next generation of antibiotics. The goal is to identify random information that affects a single species of problematic bacterium. For instance, we could potentially target S. aureus, the antibiotic-resistant bacteria that causes MRSA. We are hunting for new molecules that could destroy MRSA-related bacteria while leaving the rest of the microbiome unaffected. These experiments are underway in our lab.

Randomness may pinpoint undiscovered vulnerabilities or opportunities in plants, bacteria and other organisms. There even may be applications in solving human disease. The future is exciting as we mine the vast collections of new molecules and study how they integrate with biology to produce important desired outcomes.

Several of the molecules we’ve already identified slow plant growth. Future products from this technology might even be applied to make lawns grow more slowly. While others may find this advance helpful, I’ll have to skip using it. Cutting the grass gets my good ideas flowing.

A version of this article was originally published at The Conversation as “Can random bits of DNA lead to safe new antibiotics and herbicides?” and ran on the GLP on Sept. 27, 2017.

Kevin Folta is a plant physiology and molecular biology researcher. He currently works with farmers in order to understand agricultural technology and food security. Follow him on Twitter @kevinfolta 

Outbreak Daily Digest
Biotech Facts & Fallacies
Talking Biotech
Genetics Unzipped
ft covidresponseus feature

Video: Viewpoint: The US wrote the global playbook on the coronavirus and then ignored it

A year ago, the United States was regarded as the country best prepared for a pandemic. Our government had spent ...
mag insects image superjumbo v

Disaster interrupted: Which farming system better preserves insect populations: Organic or conventional?

A three-year run of fragmentary Armageddon-like studies had primed the journalism pumps and settled the media framing about the future ...
dead bee desolate city

Are we facing an ‘Insect Apocalypse’ caused by ‘intensive, industrial’ farming and agricultural chemicals? The media say yes; Science says ‘no’

The media call it the “Insect Apocalypse”. In the past three years, the phrase has become an accepted truth of ...
globalmethanebudget globalcarbonproject cropped x

Infographic: Cows cause climate change? Agriculture scientist says ‘belching bovines’ get too much blame

A recent interview by Caroline Stocks, a UK journalist who writes about food, agriculture and the environment, of air quality ...
organic hillside sweet corn x

Organic v conventional using GMOs: Which is the more sustainable farming?

Many consumers spend more for organic food to avoid genetically modified products in part because they believe that “industrial agriculture” ...
benjamin franklin x

Are most GMO safety studies funded by industry?

The assertion that biotech companies do the research and the government just signs off on it is false ...
gmo corn field x

Do GMO Bt (insect-resistant) crops pose a threat to human health or the environment?

Bt is a bacterium found organically in the soil. It is extremely effective in repelling or killing target insects but ...

Environmental Working Group: EWG challenges safety of GMOs, food pesticide residues

Known by some as the "Environmental Worrying Group," EWG lobbies for tighter GMO legislation and famously puts out annual "dirty dozen" list of fruits and ...
m hansen

Michael Hansen: Architect of Consumers Union ongoing anti-GMO campaign

Michael K. Hansen (born 1956) is thought by critics to be the prime mover behind the ongoing campaign against agricultural biotechnology at Consumer Reports. He is an ...
News on human & agricultural genetics and biotechnology delivered to your inbox.
Optional. Mail on special occasions.
Send this to a friend