Hacker News Reader

Comment by mirimir | Hacker News Reader

As is often the case with titles like this, the answer is that all life doesn't use the same 20 amino acids.

For example:

Akaogi et al. (2006) Role of non-protein amino acid L-canavanine in autoimmunity. Autoimmun Rev. 5(6):429-35. https://www.ncbi.nlm.nih.gov/pubmed/16890899

Nunn et al. (2010) Toxicity of non-protein amino acids to humans and domestic animals. Nat Prod Commun. 5(3):485-504. https://www.ncbi.nlm.nih.gov/pubmed/20420333

View on HN

Super interesting example! Nevertheless, even the organisms referenced in these papers don't have these amino acids in their DNA structure, and the meaning of the linked research really isn't affected by the point you are raising.

Perhaps "non-proteinogenic" is a poor choice, or not exactly correct, but readers generally understand what is meant.

It's a bit like responding to an article about "why do all pendulums keep the same frequency as they lose energy" with "but they are neglecting relativity!". It just isn't really relevant to the research question, which is "why are some amino acids present in the DNA code, and why is there consistency across species".

I'm not sure what you mean by "don't have these amino acids in their DNA structure". There are 64 codons that code for amino acids and start/stop signals. But there are only 20 common amino acids, so multiple codons typically code for the same amino acid. However, just exactly what happens depends on the set of tRNAs that are being expressed. Plus the enzymes that catalyze attachment of amino acids to tRNAs.

That is, what's in the DNA is codons, and what amino acids get incorporated depends on tRNAs etc, plus what amino acids are around (synthesized or ingested).

Anyway, I get that I was being a little pedantic. But in the paper referenced by TFA, I see that they studied three nonproteinaceous amino acids: ornithine, 2,4-diaminobutyric acid, and 2,3-diaminopropionic acid. Canavanine is much closer to arginine, with a methylene replaced with an ether bridge. I wonder how well it would have polymerized.

0) https://www.pnas.org/content/116/33/16338

Edit: Upon reflection, "there are just 20 proteinaceous amino acids" and "AS/400 is a database" are ~similar simplifications.

> non-protein

The title, of course, refers to the 20 proteinogenic amino acids.

Even then it's an oversimplification.

Selenocysteine (https://en.wikipedia.org/wiki/Selenocysteine) occurs in proteins and is quite widespread. "Selenocysteine: the 21st amino acid." (https://www.ncbi.nlm.nih.gov/pubmed/1828528) It shows up in humans too (https://www.ncbi.nlm.nih.gov/pubmed/24194593).

Pyrrolysine (https://en.wikipedia.org/wiki/Pyrrolysine) occurs in proteins in archaea and bacteria. "A new UAG-encoded residue in the structure of a methanogen methyltransferase." (https://www.ncbi.nlm.nih.gov/pubmed/12029132)

Also wasn't the answer always going to be they simply out-competed the other amino acids for that particular role? The research question is why they beat out similarly structured acids to become the consistently dominant ones in life.

So in that context the fact they are so dominant is the key part of the question, not that they are the only ones capable?

> wasn't the answer always going to be they simply out competed the other amino acids

This is a tautological statement: the ones that still exist by definition are the ones which outcompeted the alternatives, because that's what outcompeting means.

The question being addressed by the study is roughly "by what selection criterion did the survivors outcompete the others?"

Sure, my point is the fact that others are still capable of competing can always be assumed in a competitive environment. So in that context, where the question is inherently going to be why did these 20 amino acids out-compete the others, why bring up the fact others exist as a counter-point if the they aren't as dominant as the 20 primary ones? What's interesting is their dominance, not that they can play the game.

I guess it's just nitpicking the headline and is not particularly relevant to the article or the research question (as the OP admitted).

My girlfriend is a biologist and this kind of misunderstanding is IMHO the fundamental difference between a biologist and a programmer. Biology is way fuzzier than computers and that's always the default stance.

Agreed, I took an online "great courses" in chemistry and I had so many "but why?" questions I had to stop. I was spending far too long going down Wikipedia rabbit holes. You need to have a particular tolerance for not understanding it all and work with a sort of bayesian estimation of understanding as you move forward.

That's actually why I switched from physical chemistry to biology. I'm not good with abstract math, and I didn't want to be stuck relying on theoretical stuff that I didn't understand completely.

But TFA isn't about biology. At least, primarily. It's about emulating chemistry that led to the first life forms.

I did admit to being a little pedantic.

But upon reflection, it's arguable that the paper would have been more interesting if they had included L-canavanine, in addition to L-arginine and three analogs with shorter cationic side chains. Because we know that it can be incorporated during protein synthesis, in place of L-arginine. But none of their analogs can.

So if L-canavanine had been incorporated into peptides in their tests, more or less as well as L-arginine, that would arguably have ruled out their hypothesis.

I'll defer to you on that, you seem more informed on the subject than me. Makes me want to revisit my biology reading list.

Except that some sorts of life, such as some sprouting plants, do incorporate those "non-proteinogenic" amino acids into proteins.

Which then screw up animals that eat them. Because they, in turn, also incorporate them into proteins. And those tweaked proteins elicit immune responses, because they weren't present during immune system development. And some of that immune response cross reacts with the normal host proteins. So you get autoimmune disease.

This turned out to be an incredibly interesting (and educational) diversion!

It seems these amino acids aren't typically incorporated, but rather appear to serve as defense (https://www.ncbi.nlm.nih.gov/pubmed/21529857) and signaling molecules (https://www.ncbi.nlm.nih.gov/pubmed/28218981). Apparently humans do that sometimes as well (https://www.ncbi.nlm.nih.gov/pubmed/18828673). Sometimes the insects even end up using the toxic compound (in the linked example the non-protein amino acid L-DOPA) for their own purposes (https://www.ncbi.nlm.nih.gov/pubmed/27006098), which I find quite amusing.

More than just being eaten, apparently L-DOPA is released into the environment at an impressive rate in some cases (https://www.ncbi.nlm.nih.gov/pubmed/24598311).

Yes, I was wrong about that. Alfalfa seeds and sprouts don't themselves use canavanine in their proteins. And yes, plants do seriously get into chemical warfare.

While somewhat true, essentially the question of 20 amino acids still holds and trying to answer it is still meaningful (and in the same way article addresses it). Consider this: how old are these plant insecticides (or whatever they are)? Maybe some 150 mln years old? (I'm only assuming, of course, but it seems like a plausible assumption.) Well, the life on Earth itself is about 3.5 bln years old, and as far as we know it mostly utilizes the same set of 20 proteinogenic amino acids it did back then. It is only natural that given time, constantly mutating and evolving organisms would eventually learn to produce whatever amino acids possible, if it is useful (and being insecticide is obviously useful, if you are a plant, and for reasons you mention yourself it is natural to use as insecticide some compound that is not normally utilized in the other organism). The question is how did it occur that these amino acids weren't present during immune system development? Why it was always the same 20?

Yup and those shared articles don’t make a good counterargument or point..They are off topic. A better article(s) would have addressed the point of the number of amino acids...

Are you talking about human autoimmune disease? If so, do you have an examples and/or links to papers? I've read a lot about autoimmune diseases, and this hypothesis is not something I've ever heard of.

Edit: I see your earlier comment has some links. Thanks.

Yeah, some sprouts are ~dangerous. That is, if you're unlucky to have an immune system that got self-deselected in the "wrong" way.

That makes lots of sense. Do you have any examples of sprouting plants that so this? I'm guessing ones we consider poisonous?

woah that sounds interesting. Do you have some links to videos or articles which talk more about this?

articles like this are really talking about a standard that covers 99.9% of cases, not some sort of universal absolute. We know of many special cases which violate the standard (to the extent that 'life' has 'standards') but it's not clear how valuable it is to point out the exceptions here.

I don’t see your point. Could you elaborate some more?

Please see my reply to Sharlin.

Reply on news.ycombinator.com