Well, I spent the holiday weekend here sending out pictures of food on my Twitter account, so I suppose it’s only fitting that I blog about a related topic today. But it also touches on metabolic enzymes, transcription factors, and death by cyanide, so there’s something for most everyone.
I refer to this paper which appeared recently in Science, where a multinational team (Spain, Denmark, Italy, Switzerland) reveals something that’s been a puzzle for a long time: how did almonds manage to get domesticated? There’s evidence for almond consumption by humans going back thousands of years, and the details are still being worked out. But what’s for sure is that typical wild almonds are not fit to eat. They’re bitter, for one thing, and they’ll kill you even if for some reason you don’t mind the taste (5 to 10 of them could be fatal to a small child). The bitterness is from amygdalin, a cyanogenic glycoside found in a number of related plant species (for example, the pits of peaches and apricots). Those are toxic, too – there are ancient Egyptian records of the capital penalty of “death by peach”, for example – but since no one is tempted to eat peach pits rather than the peach fruit, it’s not much of a problem. Almonds, though, feature the seed as the edible part itself, which is unique among the edible Rosaceae species.
Amygdalin breaks down pretty readily – it’s a cyanohydrin of benzaldehyde and a molecule of gentebiose (glucose disaccharide), and crushing up the kernals (as in eating them!) liberates beta-glucosidase that cleaves off the sugar molecules. What you’re left with is after enzymatic cleavage is benzaldehyde, its cyanohydrin (mandelonitrile), and some free HCN floating around – with more to come, unfortunately, if you’ve swallowed the stuff. The mixture can be processed to edible almond syrup (orgeat), or almond extract, which are basically edible preparations of benzaldehyde, but you have to know what you’re doing. As with cassava (which also contains cyanogenic glycosides), local cultures worked out ways to treat the plant material to render it nonlethal, but it would of course be a bit more straightforward if the stuff weren’t poisonous to begin with.
Enter the sweet almond. But how? This is a mutant form of the almond tree that doesn’t produce the cyanogeneic glycosides, and these are (of course) the almonds you’ve been consuming all your life. This cultivar spread throughout much of the ancient world. Almond trees start bearing relatively soon compared to (say) the occasional sweet-acorn oak tree mutants known in the wild (no cyanide there, just bitterness), and were thus domesticated rapidly. In modern times, the “Sk” gene locus (“sweet kernal”) had been worked out to a fuzzy level of detail, but the complications of plant genetics left its real identity unknown. Until now. This new paper reports a draft genome of the cultivated almond, and shows that there’s actually a transcription factor mutation (bHLH2) that does the trick.
Transcription factor fans will note from that name that it’s a basic helix-loop-helix protein, which work by dimerizing through leucine-zipper interactions to form active transcriptional complexes. The mutation in this case lead to a Phe-for-Leu and Arg-for-Leu, mutations, which cause enough problems (especially the first one) to make the protein transcriptionally incompetent. Downstream of that, two CYP p450 enzymes are no longer expressed that are crucial to amygdalin synthesis (they do the phenylalanine-to-mandelonitrile part, via phenylacetaldehyde oxime). So in the end, we owe edible almonds to a change in a single amino acid side chain. This sort of mutation has surely popped up in the wild from time to time, but you’d expect it to be pretty strongly selected against, since such a plant’s seeds will tend to get eaten rather than be allowed to sprout. Until we came along, that is.
I like the fact that this paper directly cites Pliny the Elder (I wonder how many cites he picks up these days) about Roman technique of detoxifying bitter almonds, but of course he also mentions the sweet ones, albeit noting that they’re less medicinal. Bitter almond extract has been used up to modern times as a remedy, but if it’s not processed sufficiently it can have significant amounts of cyanide in it – and if it is processed well, it’s just benzaldehyde. Meanwhile, mention of medicinal effects compels me to note that the mono-glucose form of amygdalin is (infamously) known as laetrile, which is still being hawked to the desperate and/or the gullible as a supposed cancer cure. It’s useless. It’s been shown to be useless over and over, but it’s still out there, sadly, shortening the lives of its consumers and removing their money in the process. Stick with the almonds that don’t make cyanide!