Nature’s chemical warfare: an evolving struggle

Cross posted from Island Press Field Notes

The story of the black swallowtail and Queen Anne’s lace is really the story of one of the premier chemical defense systems known. These are the cytochrome P450s, or CYPs, and we now know there are thousands of different CYPs across all kingdoms of life. Every one of us relies on several dozen CYPs to metabolize chemicals that we either produce ourselves or ingest. And so whether we are tossing back some Tylenol, sipping coffee, or are experiencing a hormonal surge, our CYPs keep both essential and toxic chemicals in check.

It’s believed that the ancestral or first CYPs may have played a role in both producing sterols (chemicals with an important role in cell membranes and eventually steroid hormone production,) and in destroying sterols. As to the early role of sterols, some have suggested that they could have served as toxic deterrents for predators, turning a tasty meal into a potentially lethal tidbit, or as “chemical messengers” enabling communication between or within cells or as Queen Anne's Lace by Flickr user gb_packardsdumping ground for toxic oxygen – but that’s another story. In either case, if you have an enzyme that already interacts with the sterol, helping to produce or activate them, it’s not a stretch to think it could also help to deactivate – with a little tweaking.

Whatever the evolutionary history of CYPs may be, these enzymes are now integral to making and deactivating a diversity of chemicals and are key actors in a chemical war which has been ongoing ever since there were plants and animals interested in eating those plants – which brings us back to swallowtails.

Some black swallowtails are partial to certain umbelliferous plants (a family of plants including Queen Anne’s lace, and giant hogweed) which are poisonous to many other insects, yet the swallowtail caterpillar can feed upon with impunity. The offending chemical is referred to as a furanocoumarin, and the caterpillar’s counter defense is known as CYP6, an interesting family of CYP enzymes in insects known to be particularly highly “evolvable” and which in this case appears to have evolved the capacity to detoxify furanocoumarins.

Evolvability is an interesting concept. There are many papers and books attempting to define the term, but the gist is that it has to do with the rate of change in a particular region of DNA or gene leading to heritable changes in phenotype upon which selection can act. No one knows quite what makes a gene or set of genes more evolvable than another – you can image that some are highly conserved and need to stay the way they are – like those involved in DNA Giant Hogweed by Flickr user Kris Elshoutreplication and correction, or for oxygen-users enzymes involved in photosynthesis or detoxification of oxygen – while others are freer to change. CYPs are masters when it comes to evolving and as discussed earlier, these enzymes have become indispensable in each and every cell in our bodies and some of these, just like those of the swallowtails, are essential defensive weapons when it comes to ingesting plant, or plant-derived chemicals including many pharmaceuticals. We too, like the swallowtail, may ingest furanocoumarins only the outcome of the interaction with our CYPs is quite different.

In addition to the Queen’s lace, and giant hogweed, furanocoumarins occur in foods we may consume every day, like grapefruits. Yet rather than being rendered harmless, in some people, these plant chemicals can cause a potentially life-threatening situation by inhibiting grapefruit juice by Flickr user kylewmCYPs involved in the metabolism of common drugs including the blood thinner, Coumadin.  Years ago, before this interaction was well known, my father was prescribed Coumadin after suffering a transient stroke. All was well, until he developed a passion for grapefruit juice, and inadvertently became a text-book example of CYP associated drug interactions as the furanocoumarinsinhibited the CYPs involved in Coumadin breakdown (or, detoxification). This is now a well documented interaction, and physicians and pharmacists warn Coumadin users of the many foods which may interfere with the drug.

The story and history of the CYPs and their key role in drug, chemical and plant pesticide metabolism, is just one example of how tracing the evolutionary history may help better understand how life responds to potentially toxic chemicals, whether naturally occurring or plant derived chemicals in the case of many pharmaceuticals or synthetic industrial chemicals. Stay tuned for more.

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