A recent study brings to mind the English proverb “Enough is as good as a feast.” Sometimes “enough” can save your life if you are a woodrat forced to dine on Juniper. The study also provides a couple of nice examples of life’s response to biologically produced toxins in the context of the endless war between plants and animals. The study, by Denise Dearing and colleagues, published in Functional Ecology in 2011, compared the dining habits of two different species of desert woodrats. One species, “the specialist” (Stephen’s woodrat) normally feeds on Juniper monosperma (or J. monosperma). Juniper foliage and “berries” known to some of us for their fragrance or for their role in gin production are also laced with chemicals including alpha-pinene which is toxic to mice, men, and microbes (oh yeah, rats too). The other rat species is a “generalist” (the white-throated woodrat) which has a much more varied diet. While Stephen’s woodrat is quite capable of detoxifying alpha-pinene (see discussion below for more on that) what interested Dearing and colleagues’ was how the generalist – who must encounter many different plant toxins – manage. Do they have a greater diversity of detoxification enzymes? Or is there something else?
The results of their 15-day feeding study provide food for thought for the evolutionary minded toxicologist. Dearing’s group found that while Stephen’s rat could chow on Juniper-laced bunny food with impunity , the white-throated rats seemed to practice moderation – essentially putting themselves on a diet – less food, more water thereby avoiding toxicity. Smart little buggers. So how do they know? Perhaps, suggests Dearing through receptors in their gut which might respond more generally to certain toxics.
From Torregrossa et al., 2011:
The ability to maintain a constant PSC [plant secondary compound] intake suggest that the generalist was capable of detecting the concentration of alpha-pinene in the diet and regulating intake in accordance with a physiologically acceptable level.
So not only do we have enzymes capable of metabolizing toxics, but for those who may encounter a broader variety of toxicants in their diet, perhaps the gut can tell them when to stop (if only we had receptors which identified processed sugars as toxic chemicals.)
Now, back to those enzymes. Back in 2004, John Lamb and colleagues reported increased expression of detoxification enzymes in Stephen’s rats. In the introduction to their publication they invoked an earlier paper by WJ Feeland and Danial Janzen published in 1974, on the “Strategies of herbivory in mammals: the role of plant secondary compounds” which has since been cited over 900 times:
In their seminal article on plant secondary compounds and mammalian detoxification, Freeland and Janzen (1974) proposed that “If mammals are to eat plants containing secondary compounds, and avoid serious loss of fitness, they must possess a mechanism or mechanisms that protect them from severe physiological disturbances.” Our research focused on detoxification mechanisms that may facilitate consumption of the toxic plant, J. monosperma by the specialist herbivore species, N. stephensi. …
Lamb and colleagues found that there were indeed increased concentrations of enzymes associated with detoxification (these would be the CYPs,) in the Stephen’s rats in contrast to the “control” species, the quintessential lab-rat the Sprague-Dawley. In particular Lamb’s group found CYPs belonging to the CYP2B and CYP3A families (both of which are important for metabolism of plant-derived drugs in humans.) So, is there a genetic basis for increased concentrations in Stephen’s rats, or, would a Sprague-Dawley born to a gin-drinking juniper consuming mother, behave similarly? Or, how quickly might a generalist become a specialist? I haven’t dug too deeply, but it does appear that these differences stretch further back, beyond a generation or two (which would eliminate an argument for plasticity – though one could argue for some role of plasticity along the way.) The evolution and flexibility of CYPs is ever fascinating – and relevant – particularly as humans insist on consuming ever increasing amounts of plant-based toxicants, particularly in the form of drugs.