Selector of Improbable Mutations

A paper in the most recent Proceedings of the National Academy of Sciences examines in detail how one weed, Amaranthus tuberculatus (waterhemp) developed resistance to a class of herbicides called protoporphyrinogen oxidase inhibitors. PPO is the last, vital enzyme step in the pathway that leads to chlorophyll, the green pigment that enables plants to convert sunlight into more user-friendly energy.

Waterhemp’s resistance is remarkable on two counts; First, it involves the loss of not one but two targets for the weedkiller. Secondly, the mutation that delivers resistance is the loss of a complete amino acid in the target. Resistance mutations generally involve a change to a single letter of the DNA code. Waterhemp has lost three whole letters, an entire amino acid.

A commentary by Jonathan Gressel and Avraham Levy explains the science at a slightly more accessible level than the waterhemp paper itself, but it does much more. It makes plain just how effective agriculture is as “the selector of improbable mutations”.

Selection is a numbers game. Scientists do an experiment. They expose roughly four seedlings each from 250,000 parents to herbicide A. Not one -- out a million -- is resistant. For a different herbicide B, about 30 in a million are resistant. In the field too, some 95 species are resistant to herbicide B. The scientists declare that resistance to herbicide A, by comparison, is highly unlikely to occur in the field.

But it did. At the last count 10 species were known to be resistant to herbicide A.¹

Gressel and Levy run the numbers. Amaranthus species can dump in excess of 600 million seeds per hectare if uncontrolled. Even with continuous herbicide treatment the seedbank is around 200 million seeds per hectare. Some herbicides are routinely used on more than a million hectares every year. That’s an experiment on 100,000,000,000,000 seeds a year, give or take. A one in a billion chance of a mutation seems negligibly small. Two mutations, one in a billion billion, effectively zero. But it happened.

Nor is that the only example. Triazine herbicides effectively fry the plant. On a sunny day the herbicide blocks photosynthesis, which leads to a build-up of active oxygen that cooks the leaf. Chlorophyll is packaged into vessels called chloroplasts. Every photosynthetic cell contains many chloroplasts, and every chloroplast contains many copies of the DNA. For a plant to be resistant, every single DNA molecule in every chloroplast in every cell has to be resistant to triazine. How often does such a plant arise? To be honest, nobody has the faintest clue. Very, very seldom. But often enough that this is the second-most common form of resistance, with at least 65 species covering millions of hectares.

Gressel and Levy have this to say:

The repeated use of a herbicide on millions of hectares annually can do what we are unable to do in the laboratory with higher plants.

The PPO inhibitor herbicides were first commercialised in the 1960s, but they were never as widely used as other types, which may be why resistance took so long to evolve. But now that it has, one of the only ways to control waterhemp, especially in soybeans where it is a major pest, will be to use glyphosate and soybeans engineered to resist it.

How long before waterhemp is resistant to both types of herbicide?