The Chiral Puzzle of Life | Hacker News Reader

The Chiral Puzzle of Life

iopscience.iop.org

101 pointsbookofjoe41 comments

Perhaps there is slightly slightly different ground energy state of the two different chiralities and Nature selected the slightly lower one. I have not seen evidence supporting this hypothesis.

A similar mystery is why DNA chose a base64 nucleic coding system for 21 amino acids and a few punctuations. Some of the codons are redundant and some unused. (There appears to be a fossil base16 coding system inside it.) And synthetic biologists have modified it into a working base216 system with additional nucleic acids and amino acids. Perhaps again there is some ground energy argument as to why this universal 3-billion year old coding system is as complex as it is and no more complex.

base216? Not base256?

Probably 6^3 compared to the original 4^3, by introducing two new nucleic acids beyond A,C,G,T, and keeping the codon size fixed at 3.

Huh. DNA is like an x86.

If selection of basepairs came first (which is implied by RNA world hypothesis), then base 64 is the minimal encoding length for 21 amino acids + signalling. The question of why isn't it more complex becomes slightly moot - it's as simple as it can be given constraints. The question is why it isn't simpler then becomes asking why we have 21 amino acids.

Also not all DNA mutations produced by DNA damage are equally common, and some of the redundancy lessens their deleterious effect.

One hypothesis around the 20 amino acids relates to optimization of a quantum search algorithm [0]. Some recent work has added support to this idea [1].

[0] https://arxiv.org/abs/quant-ph/0002037 [1] https://www.technologyreview.com/2019/09/12/133081/an-import...

That does not seem a good paper. The only references on biology are quite generic books. Also the stated hypotheses are quite unfounded. As far as I know, there is barely any evidence of biology using quantum phenomena directly, except perhaps regarding photosynthesis and enzymatic activity:

https://en.m.wikipedia.org/wiki/Quantum_biology

> A similar mystery is why DNA chose a base64 nucleic coding system for 21 amino acids and a few punctuations.

This implies a kind of Cambrian explosion of coding systems for nature to "choose" from. Maybe xenogenetics will help us recognize its remnants.

As my father pointed out to a younger me, 'Evolution is lazy. It would always rather repurpose something already created than build something new from scratch.'

So, why base64? Because there was already a nice base64 library in the evolutionary repo...

> Some of the codons are redundant and some unused.

I recall reading about a paper some 10 or 20 years ago where they simulated different codon mappings and tested them for resistance to genetic mutations. IIRC they found that what we got is fairly close to optimal, in terms of which codons are redundant and to what degree etc.

One unmentioned reason is due to DNA needing a proper folding shape and polarity for the accompanying enzymes to work correctly. Imagine a sequence where one codon causes a kink or part of the DNA strand to get stuck to another section. The working version would be another variant (with a different polarity, say, due to different nucleobases) resolving the earlier mechanical issue.

Back in uni, I found it deeply unsettling to learn that the weak interaction violates parity symmetry. It feels like a glaring aesthetic flaw in an otherwise very elegant physical “design”, so to speak.

Reference for those interested in reading more: https://en.wikipedia.org/wiki/Weak_interaction

Can this be explained in more detail for those outside of physics...

Minutephysics has an excellent explanation:

https://www.youtube.com/watch?v=Elt0Gt9Cb6Q

Would you rather live in a perfectly symmetric universe without any matter in it?

It's strange that the weak force violates parity symmetry, and it's also strange that charge–parity symmetry, taken together, is much closer to being conserved but is still violated a little bit.

Is P violation required for matter creation?

Asimov wrote a book on the subject: https://en.wikipedia.org/wiki/The_Left_Hand_of_the_Electron

The origin of homochiral building blocks (amino acids, sugars) is certainly an old mystery. But it doesn't seem to be a very deep one. By that I mean that there are many physical processes that could have initially led to a small preference. Natural selection then would do the rest.

The deeper mystery is how self-replicating chemical systems ever came about in the first place. There are several fairly steep hurdles to overcome, and so far nobody has put forward a compelling, testable hypothesis leading from the "primordial soup" to anything even distantly resembling the simplest organisms.

There are many hypotheses but they are quite hard to test. The problem is that any such process is likely to have involved millions of years (at a minimum) of essentially random search among initial building blocks before something "takes."

How do you even try to replicate that? We could perhaps fast forward it in a lab but that is going to make it contrived.

The best we can probably do is to work backward from the simplest life to a credible model of prebiotic replicating molecular systems and then back from there to random organics plus energy. Then try to do isolated experiments to assign probability bounds and then try to estimate time and probability. This is not a true replication or a direct observation but it could at least provide a credible model.

I remember a coherent-sounding (to a somewhat smart layman) theory being presented in "The Vital Question". It involved alkaline vents (like these: [0]). As I remember it, the idea was that the nonviolent flow of matter and the porous rock of the vent created a natural chemical reactor, where gunk could accumulate in the pores, until it slowly chanced into a primitive pump, primitive membrane and primitive division; eventually, some of that gunk learned how to close a membrane around itself, with stuff from the alkaline vent on the inside, and could now survive out in the open, continuously pumping to keep the gradient. Evolution continued from there.

[0] - https://en.wikipedia.org/wiki/Lost_City_Hydrothermal_Field

Is it not pure speculation to assume that the world was present before living beings inhabited it? Who made these observations of a purely physicalist realm that predates beings with awareness? It may be true, but its unconfirmable, so we have to ask questions about what we can confirm. Chirality in the present is confirmable. A world made of physical matter and mind is confirmable. But strong questions about ontological declarations of life from purely physicalist material speculative histories are not only hard to answer, they assume more than they reveal.

  Edit: must have hit a nerve

I don't think you hit a nerve; your post is not only confusing, but it seems wrong.

> Is it not pure speculation to assume that the world was present before living beings inhabited it?

You need to carefully define terms here. What do you mean by "world," what do you mean by "living beings," and what do you mean by "inhabited." In any case, the answer to the question you pose is almost certainly answerable in the negative.

> But strong questions about ontological declarations of life from purely physicalist material speculative histories are not only hard to answer, they assume more than they reveal.

I'm not a materialist, but this isn't correct. In fact, a major criticism of physicalism is that it's too reductive -- not that it has no explanatory power. It has a lot of it; that's partly why most professional philosophers are materialists.

Nobody's making that assumption. It's a hypothesis.

All evidence we have is consistent with a "world being present before living beings inhabited it".

Therefore the hypothesis is not disproved, which is all science ultimately says about facts.

Chirality is either an underlying property of biological life, or an epigenetic (so-to-speak) result from having a Spinning Something and then throwing Life into it. Reality itself could have a spin or orientation and therefore Biological Life would be subservient to such. In my opinion long-term adaptations have about as much pertinence to chirality as it does to magnetism. Either it turns or it doesn't, it doesn't slowly decide to over millions of years.

RNA-world seems pretty compelling to me.

Self replication and catalysis. That sounds like enough to go on.

how self-replicating chemical systems ever came about in the first place

I don't think it's too much of a stretch to say that it's pretty much inevitable after Miller-Urey [1]. This process produces so much complexity from such simple ingredients. I think if we could travel to distant stars we would find simple, single-celled life all over the place. The tougher question is why we haven't found any intelligent life yet [2].

[1] https://en.wikipedia.org/wiki/Miller–Urey_experiment

[2] https://en.wikipedia.org/wiki/Fermi_paradox

We've only been looking for a gnat's blink, astronomically speaking. Once we've searched for a couple of million years, then we'll have a bit more data to draw conclusions from.

>a small, but persistent, chiral bias

>If this mechanism dominates, then the handedness of living systems should be universal.

No matter how large the bias (unless it's "astronomically" close to 1), there will be, by the law of large numbers, some world populated by life of the opposite chirality to the favoured one, due to it arriving first there, given the size of the universe.

Yup I don't think the author meant that all life in the entire universe must be the same chirality, just that the bias would be widespread across the universe

Yeah, it'd be interesting to see what the last graph (Figure B4) looks like if you start with mostly evil molecules rather than a racemic mixture. Maybe the bias still flips it to all live molecules after some time, but maybe it takes so long that by then somebody's gotten good at replicating the evil molecules and they end up winning.

That's a really interesting idea that cosmic rays caused the chiral asymmetry. Any biologists want to chime in on how this fits in with other ideas on the problem?

That's honestly more a question for physicists and chemists. Biologists in my experience take a lot for granted because they don't really understand the fundamentals on small scales.

The story of Thalidomide and its effects on birth defects is a good story about the chirality of molecules and their significance. The same molecule on 2d paper suddenly becomes a teratogen when the racemic mixture is given (50/50 mix of the “right hand” and “left hand” versions.) When a simple molecule like this drug with only a single chiral center at the base of so many issues, imagine a protein with hundreds or thousands of chital centers and the potential effects (or lack of effect at all) with simple changes.

Your point on complexity is well taken.

I'd just like to recommend against using thalidomide as an example of chiral effects. Rather unusually, thalidomide has a nitrogen atom as its chiral center. As such, it rapidly racemizes (interconverts) at physiological pH. This makes the claim of stereospecific teratogenicity a bit puzzling as it shouldn't be possible to resolve by administering enantiopure thalidomide.

The mechanistic story of thalidomide is a bit complicated. Ultimately the mouse and rat models used couldn't possibly predict teratogencitiy as these models have an amino acid mutation (valine -> isoleucine) that prevents binding of thalidomide to Cereblon, the protein that mediates thalidomide's teratogencitiy [0]. Amazingly, although this story is oft-repeated, its origins are unclear. This is likely the origin of the myth [1], but knowing what we know now these results should be impossible.

[0] https://elifesciences.org/articles/38430 [1] https://pubmed.ncbi.nlm.nih.gov/583234/

There's a bit of a callout to the handed chirality of life on Earth in Daniel Suarez' "Change Agent" https://www.amazon.com/Change-Agent-Daniel-Suarez/dp/1101984...

Like all of his books, it's a quick read that feels a bit like a movie screenplay. Fast and fun, each book of his has a well-enough-developed hook, but overall I liked Daemon and Freedom best.

Non-chiral protein life (as we know it) simply cannot exist, as enzymes rely on precise molecular shaping to implement the catalytic pathways for chemical reactions essential to life. Without chiral selection, it would be impossible to build these precisely folded polypeptides with well-defined functional groups.

So, for me, there is no question of “why chirality” — the entire chemical architecture of life depends on it. The question is, perhaps, “are there other options possible?”

Actually only 19 of the 20 standard amino acids are chiral. Glycine is achiral.

Is anyone working on building a mirror-image version of life in a lab? I want to know what anti-chiral chicken tastes like.

Reply on news.ycombinator.com