James and the Giant Corn Genetics: Studying the Source Code of Nature

Superman had the yellow sun of earth, spiderman had a radioactive spider-bite, but what about superweeds, where does their super power (surviving application of Round-up/glyphosate) come from?

To understand how superweeds survive, we first have to understand why normal weeds (the Jimmy Olsens and Lois Lanes of the plant world) die. <– last superhero reference of this post I promise.

Plants are not like people. The list of differences goes on and on, but today the difference we’re concerned about is where amino acids come from. Amino acids are the building blocks of proteins, the same way Adenine (A), Thymine (T), Guanine (G) and Cytosine (C) are the building blocks of DNA. Both our bodies and plants (and almost every other living thing) use the same twenty amino acids to build proteins. Our bodies can make ~12 of the twenty animo acids for themselves, but there are at least eight amino acids that the human body cannot produce (called essential amino acids). Our only source of these amino acids is from protein in our food.

It’s all well and good for us to get amino acids from our food, but plants don’t eat. They’re made of pretty much nothing more than water, sunlight and air. And trust me, none of those things are a good source of protein.

Unlike us, plants have to be able to make all twenty amino acids from scratch. That means they need whole biochemical pathways* that aren’t found in animals. But a biochemical pathway is like an assembly line. Break one of the steps in the middle and the whole thing falls apart. That’s what glyphosate/round-up does.

This part of the story starts with an enzyme called 5-enolpyruvylshikimate-3-phosphate synthase (or EPSPS for short). Do you don’t have to understand what EPSPS does specifically**, what is important is that its job is an important step in making the three amino acids Tryptophan, Phenylalanine, and Tyrosine***.  When EPSPS can’t do its job, the next protein in the biochemical pathway won’t get the parts it needs to do its job, and in short order the whole pipeline shuts down, none of those three amino acids get produced, and the plant dies.

How does glyphosate keep EPSPS from doing it’s job? It imitates one of the the chemical building blocks EPSPS normally works with, so EPSPS proteins will bind to it like they would to the actual chemical compound. But since glyphosate isn’t the compound EPSPS actually work with, it sticks in the protein. If it helps you can think of this as feeding the wrong sort of paper into a printer, causing a paper jam. Lots of individual molecules of glyphosate get into each plant cell. They stick in EPSPS proteins floating within the cell, which keeps EPSPS from doing its job, and once EPSPS stops working, the plant cell can’t make the amino acids it needs to survive, and dies.

Glyphosate is very good at doing what it does: killing plants. And as weed-killers go, it’s a lot less nasty for animals since it works by breaking a protein animals don’t need or even have. But there is one problem. Some weeds are becoming less effected by the herbicide, able to survive larger and large doses.  There are a number of ways plants can evolve to survive large doses of glyphosate. Let’s talk about three:

1. The first, and probably most obvious, is to change the shape of the EPSPS protein so glyphosate can no longer jam the mechanism. As it turns out mutations that change which amino acid is used at one specific point can produce a version of the EPSPS gene that is less likely to be broken by glyphosate. Think of it as changing the design of a print so paper that would jam the mechanism either won’t fit in the printer at all or passes through harmlessly. This method of getting “superweed” powers has been used by malaysian goose-grass and and australian ryegrass.
2. A second way for plants to become superweeds is to stop transporting glyphosate around the plant. I don’t have a good printer metaphor for this one. Cells in the leaves of plants are mostly completely grown and don’t need to make as many new proteins as the rapidly dividing cells in meristems and newly developing leaves. When a farmer sprays glyphosate it will mostly land on the mature leaves of the plant. If plants can keep the herbicide in those leaves and keep it from traveling throughout the rest of the plants, they stand a better chance of survival, and that’s exactly what has been found in resistant stiffstalk rye and pigweed.
3. The first two methods are all well and good, but I probably wouldn’t have bother to write this post if it wasn’t for the method of resistance discovered in Amaranthus palmeri (one of the many species that share the common name pigweed). Palmer amaranth’s approach to resisting glyphosate is charming in its brute force. Resistant plants have duplicated the gene for EPSPS many times (up to 160 copies in some plants!). All those extra genes mean the plants produce a lot more EPSPS protein, so no matter how many individual EPSPSs get jammed by glyphosate molecules, there are still plenty more working EPSPSs to keep doing the job, and the biochemical pathway never stops. Sure a problem with paper jams can be fixed by more advanced printers, or more strict controls on what kind of paper is allowed into the building… but Palmer amaranth’s solution was simply to build a lot more printers.

Potentially there’s potentially a fourth way to develop glyphosate resistance, which would be for the resistant version of the EPSPS protein engineered into glyphosate resistant crops**** to be introgressed into wild relatives allowing those wild crop relatives to become herbicide resistant “super weeds”. This gets talked about a lot and clearly the risk is going to depend on a lot of factors*****. In researching this post I couldn’t find any papers describing herbicide resistant weeds that owe their resistance to a gene from an herbicide resistant crop. And given how much ink has been spilled on the subject, I would expect any such papers to makes a big splash.

*Biochemical pathways are just a bunch of steps needed to get from some molecule an organism already has, to some other molecule the organism wants. Usually each individual chemical change is performed by some specific protein, like workers on an assembly line. (Sometimes its even arranged like an assembly line with intermediate molecules being passed directly from one protein to another, although it isn’t always that way)

**Although if you’re interested you can read more about the details of the EPSPS protein here.

***The first two are certainly essential amino acids. Our bodies can produce our own tyrosine, but all we do is modify phenylalanine. We can’t make it from scratch.

****Weeds that resist glyphosate are “super weeds”, but I can’t imagine ever hearing the crops that resist the exact same herbicide called “super crops” ;).

*****How the crop reproduces, whether its being grown near any wild ancestors, how weedy those wild ancestors are to begin with, which crop alleles are in close linkage with the resistance gene (crop-like traits tend to make weeds much less successful).

Gaines, T., Zhang, W., Wang, D., Bukun, B., Chisholm, S., Shaner, D., Nissen, S., Patzoldt, W., Tranel, P., Culpepper, A., Grey, T., Webster, T., Vencill, W., Sammons, R., Jiang, J., Preston, C., Leach, J., & Westra, P. (2009). Gene amplification confers glyphosate resistance in Amaranthus palmeri Proceedings of the National Academy of Sciences, 107 (3), 1029-1034 DOI: 10.1073/pnas.0906649107

POWLES, S., & PRESTON, C. (2006). Evolved Glyphosate Resistance in Plants: Biochemical and Genetic Basis of Resistance Weed Technology, 20 (2), 282-289 DOI: 10.1614/WT-04-142R.1