Friday, 7 July 2017

Pitohui ptui ptui

It's been a while since I had a piece on poison. Prevlier: Sarin - Ricin -  Botox - jellyfish - scorpionfish - diphtheria - mushrooms - so I was delighted to find out that the jungles of New Guinea host one of the few toxic birds we know about. How do we know they are toxic? Because Jack Dumbacher and museum curators experienced a tingly numbness in their fingers after handling the skins of Pitohui dichrous but not other species from the same region in their Dead Zoo. It transpires that the skin of these birds is loaded with batrachotoxin BTX, a steroidal alkaloid which had previously been isolated from the skin of frogs. Holly Grimes, while a student at Western Oregon University helpfully highlighted the characteristic steroid rings of the molecule [R]. Same core structure as testosterone and cholesterol. BTX is a neurotoxin that wedges into sodium channels in neurons making them permanently leaky. As nervous conduction depends on a delicate dance of sodium, potassium and calcium ions across the cell membrane this is severely and often fatally damaging. The LD50, injected subcutaneously into mice, is as low as 2µg/kg making it between botox and ricin in the the toxicity stakes.

Whoa, that's weird because it appears to be an example of convergent evolution where the same solution to a problem [don't try to eat me or you'll regret it] appears in totally unrelated groups of organisms. They don't look a bit alike [L] do they? And it's not just the feathers. The classic example of molecular convergence was Allan Wilson's finding that the digestive enzyme lysozyme was evolving faster in langurs Semnopithecus entellus than other primates and coming to resemble lysozymes from fore-gut fermenters like cows Bos taurus. Langurs spend their whole life chewing leaves and got better at digesting the mash when they acquired some key, cow-like, mutations.

But it turns out that neither the pitohuis nor the golden tree frogs Phyllobates terribilis,  are doing the heavy biochemical lifting in the toxin department. The frogs of the world are taking a pounding from the mills of evolution recently and  Phyllobates terribilis, are among the many amphibian species on the IUCN red listLike with White Nose Syndrome in New World bats, the immediate cause of mass frog extinctions may be the spread of a damaging fungus Batrachochytrium dendrobatidis, but climate change and habitat destruction are not helping. Ph. terribilis was not the first frog from which batrachotoxins were isolated, but it turned out to be the mother-lode, with some individual frogs containing 1 mg of the stuff. No matter how desirable the research outcome, you can't gather up handfuls of tropical frogs for destructive distillation of BTX, especially when they are endangered, so a captive breeding plan was implemented in toxicology labs. Farmed frogs had no toxin! That's when it was realised that the production of BTX is probably carried out by Melyrid beetles of the genus Choresine spp. The frogs eat the beetles and sequester the toxin in vesicles in certain cells of their epidermis for toxic recycling. It seems that the frogs have evolved a novel form of sodium channel that is immune to the effects of the poison. It is likely that the birds have achieved a similar feat. Presumably the beetles obtain the steroid building blocks from the plant stanol esters in their diet. Next question: Is there convergent evolution in the BTX-resistant sodium channels of Pitohuis and tree frogs? I think I feel an undergraduate research project coming on!

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