Living cells are biochemical systems that constantly perform chemical reactions. One of the important consequences of these chemical reactions is the capacity of a living cell to replicate itself. The daughter cells will also constantly perform chemical reactions.

From an evolutionary perspective, new cells always arise from old ones via cell division. The first cell on premordial Earth must be readily performing chemical reactions in order to replicate. A raft of biochemicals must have for some reason aggregated to form the first cell and begin chemical reactions.

An important effect of highly orchestrated chemical reactions inside a living cell is that biological order is maintained, at the expense of increased entropy in its surroundings. However, this observation is an effect of cellular organization and activities, not the cause.

I feel thermodynamics is important in explaining how a raft of biochemicals came together in the first place to organize the earliest cell, and how these biochemicals started to engage in highly orchestrated chemical reactions. Then, what is the exact theory?

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    $\begingroup$ I'm a little bit unclear on what you're trying to ask. There is a whole literature on this subject, which is normally termed abiogenesis. What is it about the standard textbook explanations of abiogenesis that you need help to understand? $\endgroup$
    – jakebeal
    Jul 16, 2021 at 18:06
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    $\begingroup$ Simple question. Simple answer. Nobody knows. $\endgroup$
    – David
    Jul 16, 2021 at 22:12
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    $\begingroup$ For a provocative paper and a great introduction to this topic, see Towards an evolutionary theory of the origin of life based on kinetics and thermodynamics, where the importance of irreversibility and autocatalysis/self-replication is emphasized. $\endgroup$
    – user338907
    Jul 17, 2021 at 19:18

1 Answer 1


The first amino acids

For how life arose from no life, the Miller-Urey Experiment demonstrates how in primordial Earth conditions, a spark in the atmosphere (analogous to lightning) could have initiated synthesis of the many of the same amino acids (and amines) life uses today.

My understanding was that the spark broke some bonds between the gases (and water vapor) in the air, allowing atoms to re-bind in new combinations to make amino acids.

Here’s a 25-Page Biographical Memoir from the NAS on Stanley Miller, page 3 is where they start discussing this experiment. Miller published this experiment in the early 1950’s, in which he identified 5 amino acids. However, NASA and others revisited the same experiment and discovered Miller under-reported amino acids present, a result from the limited equipment available at the time. They have found 14 amino acids and 5 amines. Miller’s vials from an unpublished experiment of similar nature produced 22 amino acids.

In addition, amino acids have been found on meteorites, suggesting that they are capable of spontaneous synthesis.

The first replicating life

There is a lot less known about this, as we’re still researching it now. Not only this, but there are currently several different going theories.

Keep in mind, the Central Dogma of molecular biology describes genetic flow as DNA—> RNA—> PROTEIN.

The reason why there are different theories (and so many models within them) around the chemistry-to-biology (CTB) transition does not lie in which monomer is more likely to synthesize spontaneously, rather it is almost literally a chicken-and-the-egg situation. Everything is a precursor for everything.

  • Proteins are made by amino acids, which are polymerized by metabolic processes. Proteins are made by other proteins, and directed/coded for by RNA.
  • RNA is made by the monomer building blocks of ribose (sugar), phosphate, and a base (A, U, G, C). The bases are biosynthesized from metabolic pathways. RNA is elongated, and read by proteins.
  • Metabolism is driven by proteins and largely by ATP, which contains the nucleobase adenosine found in RNA (& DNA).

Protein first

Since amino acids are the monomers of proteins, it is a likely (and simple) possibility that a spontaneous reaction bound amino acids in the right order and configuration to create the first protein that enabled life. This protein’s function could likely be to polymerize/elongate amino acid chains into proteins.

This theory is supported and demonstrated by this study, which suggests that the first “protein” catalyzed the elongation and proper folding of other amino acid chains, including creating more copies of itself. 0.3% of the possible permutations of monomer sequences give a “protein” the elongation capability described, which though small, is an exciting possibility considering the age of the Earth and timeline of life. What’s more, polypeptide formation does not require as much precision as RNA synthesis, as speculated characteristics of proteins and amino acids comport with the computer modeling shown by the study.

Though this theory seems to contradict the central dogma, we must keep in mind that thermodynamically the reactions occurring at the origins of life were spontaneous, so the “pattern” of genetic flow present in most life might not be a direct indicator of “what came first.” This is supported by the existence of prions (pathogenic proteins), and the fact that simple organisms don’t always use mRNA to synthesize proteins (alternatively, they use “nonribosomal peptide synthetases”).

The limitation of protein-first models is that proteins don’t really “work backward” into RNA. Though nucleic acids acids contain components of amino acids from their biosynthesis, the are pretty different molecules.

Some models suggest this protein-first theory, AS WELL as an RNA first theory (see below). The idea is that self-replication of biological molecules started with proteins, but nucleic acid-based “life” also evolved, seperately. RNA self-replication probably took longer to reach, but outcompeted protein “life,” explaining today’s life as well as providing an explanation for the above limitation.

Organisms can “uptake” other organisms and incorporate them into their own cells. 2 commonly-cited widespread examples include organelles mitochondria and chloroplasts, both thought to originally be independent prokaryotes themselves.

RNA first (aka The RNA World Hypothesis)

Some theories suggest RNA came before functional proteins. In fact, this has been the de facto theory, because we had no mechanism to explain how proteins could self-replicate - something that has recently been demonstrated. In addition, this follows the central dogma, and would explain not only the development protein synthesis but also genetic information storage (the latter of which cannot be directly explained by the protein-first theory alone).

An idea behind this is that some RNA was able to auto-synthesize the first RNA-replicating enzymes. This sounds like a catch-22, but this study had found some RNA strands when joined can self-create an enzyme that replicates itself - the literal chemical makeup of this enzyme are RNA-oligonucleotides. However, these RNA fragments in the lab have been take from existing ribozymes, so they may not be an accurate indicator for the first, spontaneously-created enzymes.

Limitations from and only RNA-first model stem from the fact that currently RNA synthesis/replication processes are detailed, intricate, and fragile. The chances of spontaneous reactions alone creating this process seem minuscule (though as mentioned earlier life took a LONG time to develop).

Until recently, another cited limitation concerned the fact that no known organisms replicate RNA. However, some viruses manage to code for RNA-replicated proteins, and (as mentioned earlier) RNA’s capability of self-replication has been recently discovered, be it in a lab setting.

Other theories

The last main debated theory concerns metabolism. This idea suggests metabolic processes occurred before the first life form, since many metabolic processes known today synthesize amino acids and nucleic acids from chemicals in our diet (how our body make the building blocks). However, such a huge part of what makes metabolism today possible is driven by enzymes, which are proteins. Because of this, all of these processes would have to be dramatically slowed down in rate to mimic spontaneous reactions in primordial conditions, and on top of that there would have to be an explanation for how energetically unfavorable reactions in metabolism would occur. Most of these energetically unfavorable reactions in current metabolism harvest the potential energy in ATP, which longhand is adenosine triphosphate. The molecule adenosine is also used as one of the bases in nucleic acids, which at some level inherently contributes towards to the RNA World Hypothesis.

Primordial amino acids (that have not been retained in today’s life) serving as the hidden first building blocks of life is not an uncommon theory. However, this concept rarely stands alone - it typically contributes to either the protein-first or RNA-first theories.

Proto-RNA theories propose an unknown “stepping stone” molecule like RNA. Evidence of this inherently will be limited.

Some ideas cite a meteor or space rock on which life was present collided with Earth, transferring life to Earth.

Once self-replication AND translation (RNA-protein) have been established, Darwinian evolution can explain the rest.

Additional resources

How Structure Arose in the Primordial Soup (Quantamagazine)

Life’s First Molecule Was Protein, Not RNA, New Model Suggests (Quantamagazine)

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    $\begingroup$ What simple organisms use "nonribosomal peptide synthetases” to syntheisize proteins ? $\endgroup$
    – user338907
    Jul 17, 2021 at 8:36
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    $\begingroup$ All organisms replicate RNA, do you mean self-replicate RNA? the big advantage of the RNA world hypothesis is the entire RNA to protein translation process is made of RNA components. both ribosomal subunits, tRNA, Its all RNA. proteins are made by RNA not proteins, they are modified by other proteins. you also may be interested in more recent work on self-replicating self-catalyzing RNA. ncbi.nlm.nih.gov/pmc/articles/PMC3943892 $\endgroup$
    – John
    Jul 19, 2021 at 1:31

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