[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]

I also do not believe that our RNA and complex amino acids are likely to be universal.

On the other hand, the simple amino acids are known to be universal, both from chemical analyses of celestial bodies and from abiotic syntheses in laboratories.

In theory, sugars can be produced abiotically by the polymerization of formaldehyde. However, sugars are not very stable chemically and suitable catalysts for formaldehyde polymerization seem to be rare, because sugars are much less ubiquitous than amino acids in lifeless environments.

The role of phosphorus in biology is determined entirely by the property of the phosphate anions that they can eliminate water and condense into polyphosphates, then the polyphosphates can extract water from other molecules, forcing condensation reactions, which can be used for various purposes, e.g. for building polymers.

The nucleoside parts of ATP and related substances play only the role of a "handle", which can be used to control the location of the polyphosphate parts, so that they will perform their function where intended.

Thus for controlling the polyphosphates other molecules may also be suitable.

Disulfide bonds, which already exist in the pyrite mineral, must have had a crucial role in the origin of life. But their role is very different from that of polyphosphates, because they extract hydrogen, instead of extracting water, so they perform redox reactions, not condensation/hydrolysis reactions.

Thioesters are the sulfur compounds that can play the same role as ATP, by taking part in condensation/hydrolysis reactions.

There is no doubt that all the 5 elements H, C, N, O and S, which happen to be the most abundant electronegative elements in the entire Universe, must be used by any living being, since the origin of life. Whether phosphorus has also been used since the beginning, or it is a later addition, is uncertain, because thioesters could have been used originally for performing all the functions now done with phosphates like ATP.

Both nitrogen and phosphorus are affected by similar availability problems. While nitrogen is too volatile and most of it would always have been stored in dinitrogen gas, which is inert, instead of being stored in easy to use ammonia or hydrogen cyanide molecules (while hydrogen cyanide and carbon monoxide are now toxic for most living beings, it is likely that they both are very important for the appearance of life), for phosphorus the problem is that most of it is stored in insoluble phosphate minerals. This must have been alleviated around the origin of life by the fact that the early oceans were much more acidic than today, so much more phosphate ions would have remained dissolved in sea water, than today.

Unlike for phosphorus, there is no substitute for nitrogen in biology. The role of nitrogen in organic molecules is the same as the role of dopants in semiconductor devices. When nitrogen substitutes carbon in an organic molecule, that position in the molecule becomes positively charged, instead of being electrically neutral. These electric charges play very important roles in many chemical reactions.

The poor availability of nitrogen must have been the main constraint in the growth of the early forms of life, until the development of the nitrogenase catalysts that allow the use of dinitrogen from the atmosphere.

Similarly, it is likely that the earliest forms of life used carbon from carbon monoxide, whose lower availability limited growth until the development of a catalyst that reduces carbon dioxide to formic acid, which allowed the use of the more abundant carbon dioxide. Both catalysts, which are used to capture carbon dioxide and dinitrogen, appear to have used in their earliest variants molybdenum, or possibly the related tungsten. While molybdenum seems to be a later addition to the set of chemical elements used for life, iron, cobalt and nickel are all necessary for the appearance of life as catalysts, while potassium is also necessary since the beginning for maintaining the electrical neutrality of a water solution without producing solid precipitates that would cause death.

The abilities to use directly carbon dioxide and dinitrogen, which are the main constituents of most planetary atmospheres, and which were also the main constituents of the early atmosphere of the Earth, must have greatly expanded the environments suitable for life, which previously must have been restricted to small neighborhoods of hydrothermal vents or sources of volcanic gases.

[mjanx123]

- cells appear very soon after the hadean Earth - meteorites contain life building blocks

These suggest that the life chemistry evolved in the proto solar cloud (and exploring the conditions in there would yield how that happened) and the life on Earth evolved from the already complex stuff that fell on it after the hadean phase.

[don_esteban]

Great post! Thank you.

Is it conceivable that instead of water, some other solvent can be used? Those ethane/methane lakes on Titan ...

[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-...