A Naturally Genetically Modified Organism.

This week, I’m going to write about a Genetically modified crop plant brought into the world by nature. Did you think only humans could genetically modify organisms? Nature’s been at it since long before humans were around.

An international team of researchers published a paper in PNAS about the discovery of two T-DNA loci in the genomes of domesticated varieties of sweet potatoes. The latter clause in that sentence is a bit dense and I’ll unpack it in this post.

What is a T-DNA?

T-DNA is a segment of DNA from a genus of bacteria called Agrobacterium. There are two species, tumefaciens and rhizogenes. These bacteria are plant pathogens. They cause crown gall disease in the plants they infect. The T in T-DNA stands for transfer-DNA. As part of the infection process, Agrobacterium generates a segment of DNA that it inserts into the plant genome. It’s a segment of DNA that has several genes contained within it. From there, the genes on the newly inserted T-DNA start to express themselves. Some of the genes are involved in hormone biosynthesis, auxin in particular. They also have genes to co-opt the plants metabolism to make molecules like octopines that the bacteria feeds on. And then there are genes on the T-DNA that scientists don’t fully understand the function of. The hormone imbalance causes an increase in cell division that’s not controlled, causing a mass of cells to be produced in the plant, all of which have the T-DNA creating food for the bacteria. This is what causes the gall on the infected plant.

Nature is an genetic engineer. And nucleic acids (DNA and RNA) are almost everywhere.

The T-DNA insertion is permanent in the cells where it inserts. It is a form of what scientists call horizontal gene transfer (HGT). HGT is pretty common in nature, particularly at the microscopic scale of life. Some viruses insert their DNA into genomes of infected host cells and can remain dormant there for a long time before reviving to cause infection. HIV does this. So it’s possible to be HIV positive, but not show outward signs of AIDS. Bacteria transfer DNA between themselves a lot too. Nature is a genetic engineer. And nucleic acids (DNA and RNA) are almost everywhere.

To be inherited in the next generation, the HGT has to happen in germ line cells that form the next generation (either pollen or ovules in plants). Otherwise the transfer will die with the host.

To be inherited in the next generation, the HGT has to happen in germ line cells that form the next generation (either pollen or ovules in plants). Otherwise the transfer will die with the host.

Scientists use of T-DNAs

Scientists combine cell culture technology and modern molecular, recombinant-DNA technology to have learned put any segment of DNA desired into Argobacterium and it will transfer it into many plant varieties (with some size restrictions). Once infected, individual plants are regenerated, also via cell culture methods, and tested to see if they carry the transgene (the newly inserted segment of DNA). This is the basic way scientists create GMOs. In some plants, it’s possible to just coat flowers in Agrobacterium and they will insert their T-DNA into the reproductive parts of the plant– the ovules specifically– and thus in the next generation, some plants will be transformed. The T-DNAs scientists use often contain what are called selectable markers. Either antibiotic resistance or a nutritional requirement that allow them to easily select the transgenic individuals.

The difference between wild Agrobacterium and modified Agrobacterium used by scientists as a research tool.
The difference between wild Agrobacterium (top) and modified Agrobacterium used by scientists as a research tool (bottom). The text in green/DNA sequence it represents gets transferred.

Kyndt et al. discovered in domesticated sweet potatoes there are two places where T-DNAs have stably, and heritably, inserted themselves into the genome of the “Huachano” landrace. They dubbed them IbT-DNA1 and lbT-DNA2. IbT-DNA1 appears to be universal in domesticated varieties while IbT-DNA2 is only present in a handful of domestic varieties. Neither is present in the closest wild relatives. They also find that the genes on the T-DNA are expressed (not a forgone conclusion; just because DNA is there, does not mean it is expressed/does something), suggesting they may be doing something to alter the plant’s biology, though the scientists in this report have not been able to find definitive evidence of that as yet. An attractive hypothesis is that the IbT-DNA1 insertion conferred a desirable trait to the plant that made it appealing to ancient South Americans as a candidate crop plant. T-DNAs naturally alter hormone levels; auxin and cytokinins, and so it is not inconceivable that this might cause some changes to the plant.

Kyndt et al. discovered in domesticated sweet potatoes there are two places where T-DNAs have stably, and heritably, inserted themselves into the genome of the “Huachano” landrace.

Another interesting fact in the IbT-DNA1 case insertion site is in the intron of another gene. It’s a so-called F-box gene that codes for a protein involved in targeting specific proteins for degradation. The auxin receptor is an example of an F-box protein, but there are typically hundreds of F-box genes in plant genomes. The authors don’t say whether the T-DNA disrupts the function of the F-box gene, but it may. T-DNAs landing inside genes is actually a tool for gene disruption researchers use to induce loss-of-function in genes.

What does it mean?

The fact that nature has done what humans do now— long before we even knew about DNA— does bring up the question of what’s wrong with humans doing cross-species modification. In nature, if two living things come into contact, there’s potential for an interaction or transfer. Our bodies are awash in bacteria, viruses, and if we eat plants (most of us do every day), we eat DNA, RNA and protein that make up plant life.

The fact that nature has done what humans do now— long before we even knew about DNA—does bring up the question of what’s wrong with humans doing cross-species modification.

Heritable and advantageous HGT is not the most common process; a case of potential junk DNA that will be lost over time. However, natural HGT is a part of how some new viruses emerge, for example. Another plant-to-plant example is a hornwort was the source of a gene capable of perceiving light to a fern that proved advantageous for that group of ferns. Humans can now do what nature does in a relatively controlled way. The T-DNA insertion site appears to be largely random, though with the latest generation of genome editing technology, CRISPR, it’s possible to modify genomes in a more precise way, or target an insertion. When a GM plant is made, it needs to be assessed to make sure the desired trait has been conferred stably. For instance, silencing of the transgene can occur if you express a gene product too much. And there can be genome rearrangements caused by the T-DNA. This is a hazard of causing double stranded breaks in DNA. Again, this is why GM plants are tested thoroughly. And before the process even begins, traits to confer by modification are chosen carefully, not at random. And even after its made, testing for allergenicity, environmental safety, etc. are done. The function of the genes inserted for commercial products is also well studied prior to transfer. The Bt toxin gene was well known and already used by farmers in a spray form before it became a GM crop technology.

Critics of GM technology say that it’s inherently unsafe messing with nature. That really denies that humans are part of the natural world.

Critics of GM technology say that it’s inherently unsafe messing with nature. That really denies that humans are part of the natural world. This sweet potato story suggests that nature has done essentially the same thing we have begun to do with genes that are useful for our purposes. And the fact is, we know less about what the genes on the natural T-DNAs do than we do about the genes scientists have used to make GM plants for farmers. Researchers use these technologies all the time to do our research; for instance using fluorescent proteins to tag genes of interest and track their expression. And there are attempts to make useful/better products by engineering yeast or bacteria or to have good coffee on the International Space Station. For instance, human insulin to treat type-I diabetes is produced in a genetically modified bacteria.

A good environment is not just a luxury item. It affects human health, productivity, and overall well being.

Humans, all 7 billion of us (that’s a big number), do have a responsibility to be good stewards of the planet. A good environment is not just a luxury item. It affects human health, productivity, and overall well being. And there are cases where a GM plant can provide an environmentally friendlier solution.

It is up to farmers to buy the seeds they plant. If GM were not useful for them in some way, they would not buy them. GM is not a panacea, it can’t solve every problem. And new technologies do carry some risk and need to be evaluated on a case-by-case basis (so far, all have been deemed safe by many regulatory bodies). But biotech companies know that and in fact likely err on the side of less radical products that are likely to be profitable. Biotech is expensive and resource intensive. Any failure of a product or one shown to be harmful could sink a company, even one that seems too big to fail. It’s why Monsanto does not just produce GM seeds, it also produces organic, elite varieties of plants through technology driven (read: quickly able to identify plants with desirable traits) selective breeding. It’s diversifying the product base.

The process of generating the naturally GM sweet potato and the GMO Bt-maize is identical.

The process of generating the naturally GM sweet potato and the GMO Bt-maize is identical. The inserted DNA is different. And a simple blanket statement against GM technology does not capture the complexity that GM is not one thing. GM is a process. It’s part of our tool box. And one we’re likely to need as we try to feed the projected 9 billion people that will live on Earth in 2050. As Pam Ronald said on the TED Stage:

“What scares me most about the loud arguments and misinformation about plant genetics is that the poorest people, the people who most need the technology, may be denied access because of the fears and prejudices of those who have enough to eat.”

References

Kyndt T, Quispe D, Zhai H, Jarret R, Ghislain M, Liu Q, Gheysen G, Kreuze J. 2015. The genome of cultivated sweet potatoes contains Agrobacterium T-DNAs with expressed genes: An example of a naturally transgenic food crop. PNAS: www.pnas.org/cgi/doi/10.1073/pnas.1419685112

 


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