[adrian_b]

I agree.

It seems that the choice between left-handed and right-handed amino-acids was random.

However, it is unlikely that other kinds of life forms could use both kinds indiscriminately, because mixing them creates difficulties in the assembling of polymers. So it is likely that amino-acids produced by some extra-terrestrial life form would also be predominantly of only one orientation, but it could happen to be the right-handed variant.

Moreover, extra-terrestrial life forms could use very different complex amino-acids, because there are much more of those than the 11 that have been added to the simple amino-acids in the terrestrial proteins.

[asdff]

That makes sense that the chirality can affect downstream polymer assembly or even folding in the higher order structures.

Likely we are all left handed on earth because our left handed ancestor outcompeted the right handed organisms in the primordial soup. Or the right handed organisms just didn't evolve in the first place here on earth and there was nothing to outcompete. There might still be some higher order advantages to shifting chirality one way or another. Certain molecules, such as methamphetamine, have differing bioactivity based on chirality. Maybe this can be regulated in some way such as to control the rate of some other downstream process. In an abstracted sense, chemists here on earth are already this organism as they refine reactions to produce desired chirality and reduce expenditure on undesired chirality.

ET could be using different amino acids, or more or fewer. I would hazard to guess there is immense selection to reduce the amino acid set to its most necessary components. This pressure has gotten to the point here on earth where even these necessary components might not all be produced endogenously by the organism who needs them, but consumed from the environment saving energy spent on synthesis. But this requires your neighbor to be producing these AAs, such that you consume them, and you having sufficient feedback mechanisms to not immediately consume all of your neighbor's species and put your own insufficient lineage to extinction.

[cyberax]

Life can even use something other than amino acids. They are really inconvenient when you think about it. Fixed nitrogen is extremely rare, and there are no nitrogen-containing minerals other than some exotic exceptions.

Amino acids are useful because they can be easily joined together and split apart (via the C-N bond). But there are other types of "molecular glues" that are viable, like sulfur or phosphorus.

[adrian_b]

Amino acids are much more likely to be involved in the appearance of life anywhere than other molecules.

For instance it would be much less surprising if an alien life form used another kind of polymer to store information, instead of nucleic acids, than if it would not use amino acids. The fact that on Earth the living beings eventually used ATP and RNA appears to have been determined in great part by chance, while the use of amino acids seems to have been much more deterministic.

Some of the simple amino acids are very easy to be synthesized in abiotic conditions, which is why they are ubiquitous in many celestial bodies.

The advantage of amino acids is that they do not contain only one end that can be attached to other molecules, but that they contain two such ends. A molecule with only one connector would attach to another, forming a dimer, after which no further reaction is possible.

A molecule with two connectors, like an amino acid that has both a carboxyl end and an amine end, can be daisy chained into a polymer of arbitrary length. This allows building complex structures.

There are other molecules with two connectors, but they are much more unlikely to appear in abiotic conditions.

Thioesters, i.e. a kind of organic molecules that are bound by a sulfur bridge, like you mention, appear to have been much more important when life has appeared on Earth than today, but such molecules were important as intermediates in metabolic reactions, not as structural blocks, like amino acids, and there are no known naturally-produced molecules with sulfur that could be used as easily as amino acids to make molecules with arbitrary complex shapes.

[cyberax]

> The fact that on Earth the living beings eventually used ATP and RNA appears to have been determined in great part by chance, while the use of amino acids seems to have been much more deterministic.

It looks like on Earth the RNA was the initial replicant. RNA can be folded into complex shapes and can have catalytic properties in itself. Ribosomes that assemble proteins have RNA at the active site with proteins only providing structural framework.

That's why amino acids might not end up being so universal.

[don_esteban]

There is no contradiction: simple amino acids as a basic building block being coopted by replicating RNA to build more sophisticated structures.

You can conceive other than nuclear-acids based replicant, using the same ubiquitous amino-acids to build a protein life not using RNA/DNA but some other encoding structure.

The question is what is the chemically most likely 'other'? Also, what could be alternatives for ATP/sugars?

[cyberax]

Sugars are just chains of hydrocarbons with alcohol groups, they are probably going to be ubiquitous. ATP is useful because the phosphate groups make a stable bond that nevertheless can be hydrolyzed, releasing a lot of energy.

But the adenosine "backbone" of the ATP is more-or-less arbitrary. Other forms of life can use something different. Or they might use the phosphorus bonds themselves where terrestrial life uses peptide bonds.

Disulfide bonds exhibit similar properties, and terrestrial life also uses them to give additional "rigity" to certain proteins. It's also likely a late addition to the genetic code, cysteine is nestled between two stop codons (it clearly used up the initially reserved block of the address space tagged for future expansion).

And if you look at meteorites, sulfur compounds are _much_ more common. Sulfur chemistry also doesn't require scarce fixed nitrogen that could only be replenished by lightning before nitrogen-fixing enzymes first evolved.

So I don't believe at all that exactly our RNA/amino acids are going to be universal.

[adrian_b]

RNA was indeed the initial replicant, i.e. the first molecule that contained an arbitrary sequence of blocks and which could be used as a template to generate copies at itself.

However, such a replicant could appear only after a life form with metabolism already existed.

For replicating RNA, there must exist a complex system that extracts energy from the environment and uses that energy to synthesize nucleotides like ATP and then it uses additional energy to polymerize the nucleotides into RNA.

RNA itself or any other molecule capable of replication could not have had any role in that living system, because before the existence of replication, any molecule of RNA that would have appeared accidentally would have disappeared eventually, without descendants. Therefore the first molecule of RNA that has survived must have been self-replicating and it could not have other functions.

The first self-replicating RNA molecules have diverted resources from a pre-existing living being, by consuming nucleotides like ATP, which must have already been used long before the appearance of RNA, for implementing condensation reactions.

In other worrds, the first RNA molecule, i.e. the first nucleic acid molecule was a virus. Some of the present viruses might have had their origin as detached parts from some nuclei of cellular beings, but it is likely that most viruses descend from the primordial viruses and they have never been cellular life forms.

The cellular life forms must have appeared by symbiosis between a virus and a life form without nucleic acids.

It is a frequently believed myth that life requires a memory molecule, like a nucleic acid. This is a mistake perpetuated by people unfamiliar with engineering.

It is perfectly possible to have a chemical system that growths and replicates itself, without containing any molecule able to store arbitrary information, like a nucleic acid. The difference between such a chemical system and the cellular life forms of today has the same nature as the difference between a hard-wired processor and a microprogrammed processor, i.e. the nucleic acids play the role of the microprogram memory that controls the execution units of the processor, allowing the implementation of an arbitrary behavior by changing the sequence of microinstructions, while the hard-wired processor has a fixed behavior, which can be changed only by a redesign of its structure.

Information-storage molecules like the nucleic acids are without doubt necessary for the evolution of complex living beings, because they allow the random generation of a huge number of variants that can explore the solution space, from which survival will select optimized variants. The nucleic acids have brought to living beings the same kind of flexibility that programmable embedded computers have brought to various appliances, whose properties can now be changed by a software update, instead of a costly recall and hardware redesign.

In a "hard-wired" living being, evolution must be extremely improbable, because any change in some of its component molecules is likely to break the cycle of self-replication, leading to death without descendants.

In a self-replicating chemical system, there must be a long chain of chemical reactions, each using as input reactants the products of the previous reaction, while the first reaction in the chain must use the products of the last reaction, closing the cycle.

It is very likely that in such a self-replicating chemical system, peptides, i.e. relatively short chains of amino-acids, had a very important role in providing a scaffold that organized the chain of reactions.

Even today, most if not all living beings still produce so-called non-ribosomal peptides, which, unlike the proteins, are not produced by templates of RNA.

Unlike with the mechanism of protein synthesis by ribosomes, for now the mechanisms that establish the sequence of amino acids in non-ribosomal peptides are very poorly understood.

It is likely that at least some of the mechanisms of synthesis of non-ribosomal peptides are a remnant of the synthesis mechanisms used before the appearance of RNA.

[asdff]

Some caveats with this theory is that these non ribosomal peptides are synthesized by an enzyme that itself is encoded in DNA.

But RNA alone is sufficient to template off itself and create new copies. It can fold into catalytic forms akin to folded proteins. It can even spontaneously generate into chains from the constituent monomers under certain assumed early earth conditions (1). There is a lot of literature behind this formation under various conditions. A lot of guestimates on what these conditions might translate to experimentally, but the general trend is that this seems to be possible under early earth conditions.

1. https://pubs.acs.org/doi/full/10.1021/acscentsci.5c00488

What is left is determining how the consitutent nucleotides might have formed. People have ideas on this though. This review is a bit old now but on topic at least: https://pmc.ncbi.nlm.nih.gov/articles/PMC6316623/#sec4-life-...

[adrian_b]

The living beings use much more amino acids than those that compose proteins.

The relatively low number of amino acids that are used in proteins appears to be caused by the difficulty of modifying the genetic code by adding not yet encoded amino acids to the set of encoded amino acids.

Variations of the genetic code are known at various living beings, but nonetheless they are very rare, because a change in the genetic code requires a lot of other coordinated changes. A new kind of transfer RNA must be encoded in the genome (the only likely origin of such a new tRNA is a mutation in one of the existing) and that RNA molecule must be able to bind preferentially to the codons that are repurposed to encode a new amino acid, and also to molecules of that amino acid, which requires a lot of favorable change is the molecular structure of that RNA.

It seems that in the earliest form of genetic code, there were only 4 distinct symbols, i.e. of the 3 nucleobases of a codon only the central one was meaningful and the 2 peripheral nucleobases did not encode information.

The 4 original symbols selected between 4 major kinds of amino acids: the special amino acid glycine, an acid amino acid, a hydrophobic amino acid and an amino acid with intermediate behavior, like alanine or proline.

These variations would have been enough to build proteins with specific conformations.

The fact that a codon had 3 nucleobases, presumably to ensure the binding to transfer RNA molecules, even if only one of them encoded information, appears to have been a great luck, because this allowed later the expansion of the genetic code, because 3 bases give 64 combinations allowing the encoding of up to 64 symbols.

Most of the possible codons have remained ambiguous until today, but the number of encoded amino acids has increased slowly in time, up to 21, the most recent additions to the encoded set being those of the sulfur-containing amino acids, aromatic amino acids and selenium-containing amino acids.

As you say, there are disadvantages in using many kinds of amino acids, but there are also advantages, by allowing the creation of proteins with properties that are not achievable with a smaller set of amino acids.

The balance between advantages and disadvantages appears to have slowed down continuously the rate of adding new amino acids to the set encoded in the genetic code, so that the majority of the living beings of today have not added any new amino acid since several billion years ago.

Most of the expansions of the genetic code happened before the last common ancestor of all living beings of today, so that today there are very few living beings with more recent modifications in the genetic code.

[pocksuppet]

It could also be that other forms of life produce both forms, but selectively use one.

[IAmBroom]

Wouldn't that require a constant filter, to ensure that L-processes never use R-amino compounds? Seems almost like a Maxwell's Demon would be required in every cell...

[pocksuppet]

They just can't use those compounds. Many medications have L and R forms of which only one is active. Right-methamphetamine is, well, methamphetamine, but left-methamphetamine is a nasal decongestant. Which is to say that the unwanted variation of a compound can be harmless.

Just about every molecule in every cell is already a maxwell's demon. They only fit together in specific ways.