Evolution is the transformation of species into slightly modified species. The origin of species is solved in principle. However, the origin of life is a fundamentally different problem. Darwin avoided discussing the origin of life. It is the hardest problem of biology and it still has not been solved yet. Whereas the details of evolution can be described as a puzzle, the origin of life must be characterized as an intractable problem.
A crucial step (although not the first step) in the origin of life was the invention of DNA and the Genetic Code. DNA has become a defining property of life. But how DNA acquired its meaning is still a mystery. How could a relatively chemically inert non-enzymatic molecule (DNA) become useful, even indispensable, for life? DNA itself could not have been involved in the origin of life (Think about this...). There must have been something before DNA.
In the literature the Genetic Code is usually presented as a table in which all 64 combinations of 3 bases A, T, C, G are 'associated' with 20 Amino Acids. These associations could be made in many different ways. Nature got stuck to one system of associations called the Genetic Code table. In the book The Equations of Life: How Physics Shapes Evolution, Chapter 7 'The Code of Life', physicist Charles S. Cockell notices that the Genetic Code table is non-random. This is an important observation. The assignments of base triplets to Amino Acids (AAs) is non-random. When looking at the table It is immediately clear that there is a pattern. Secondly, there is redundancy: many Amino Acids are coded by more than one base triplet. But there is also a pattern. This is all known very well.
However, Cockell also notices that there is something special about nature's choice of the twenty Amino Acids. There are many more natural Amino Acids available than those twenty. So, why those twenty? Random? Accident? Or are they the most suitable for their task? He refers to a publication [1] that argues for a non-random choice. The authors reasoned that there are 3 properties of Amino Acids that are important for constructing a protein: (1) the size of an Amino Acid, (2) the charge, (3) hydrophobicity (repelling water) [3]. Together those properties determine how the protein behaves and what it can do. In principle proteins could be constructed from one or a few Amino Acids. But most useful proteins consist of a diverse mixture of amino acids. Proteins are defined by a unique sequence of AAs to fold into a complex 3D shape. Also, it is not useful to have many AAs with the same hydrophobicity, or the same size or the same charge. The best toolkit for life would have an even distribution of AA properties that does not overlap too much. To test for optimality the authors tested a set of fifty AAs found in the Murchison meteorite. The reason? They assumed that AAs found in the meteorite would represent the set of AAs found on the early Earth. What they found was astonishing, writes Cockell:
"When they compared the twenty amino acids used by life with a million alternative bundles of amino acids randomly chosen from the fifty in the meteorite, the twenty used by life had better coverage and combinations of all three of the key factors than did any other set. ... they seemed to be selected by evolution to give a wide range and even distribution of properties that might be useful in proteins." ... Of a much expanded set of seventy-six AA, not a single group out of a million possible alternatives outperformed the natural set.". (chapter 7).
Cockell concludes that the twenty AAs used by life are not random. That was new to me. But there is one important aspect Cockell doesn't mention: the AAs must also be suitable to be attached to a transfer RNA (tRNA) and to be processed by the ribosome. This is a crucial property. It is the biochemical implementation of the Genetic Code table. There could be differences in suitability. This must be investigated. Furthermore, all AAs are associated with 1 or more triplet codons (redundancy). The question is: how is the association made between a base triplet codon and the AA? And how did that originate in the first place? The structure of tRNAs does not show a direct chemical bond between codon and AA. Is it a random choice? That could certainly be the case because AAs and triplet codons (bases A, T, C, T) are different chemical compounds, yet they are somehow connected. Or is there a logic in the associations? Is there a pattern? Much research has been done to solve this question. No definitive answer yet. Cockell does mention this. But at least he pointed out a new aspect of the origin of life and the Genetic Code table to me.
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In this blog I did focus on the origin of the Genetic Code. The origin of the Genetic Code is in fact the origin of DNA-based life: bacteria, animals and plants. It is also the origin of protein and enzyme based life. The origin of DNA and proteins are strongly intertwined. DNA on its own has no use and proteins can not exist without DNA. DNA cannot self-reproduce, it needs enzymes. But proteins cannot self-reproduce either. A specific protein consists of a unique sequence of Amino Acids. Unique proteins do not self-assemble spontaneously. The only way to reproduce such a unique sequence is on the basis of another unique sequence: the unique base sequence in DNA. In other words: DNA and proteins depend on each other. This not a promising situation to start life. Hence, the hypothetical RNA world was developed (which is not without its own problems!). Keep in mind: the origin of the Genetic Code is not the same as the origin of eukaryotes. Bacteria are also DNA- and protein-based life forms. All life on earth uses the same Genetic Code, including viruses.
Physicist Charles Cockell used the expression "DNA and its entourage" [2]. And that is a misleading description. I hope readers recognize this as DNA-centric thinking. The cell and the cellular machinery are not an "entourage"! It is an equally important part of the cell! DNA is not the master of the cell! The cell is not the servant of DNA!
Notes
- Gayle, Freeland (2011) Did evolution select a nonrandom "alphabet" of amino acids? Astrobiology
- "An entourage is a group of attendants, assistants, or close associates who accompany and work for an important or famous person".
- There exist another list of properties of AAs: polar versus non-polar; acidic versus basic. [5 May 2026]
Further Reading
- Can AI simplify the alphabet of life? Generative AI design yields functional proteins with only 19 amino acids. Science, 30 April 2026. The design functional bacterial proteins without the amino acid isoleucine.
- Toward life with a 19–amino acid alphabet through generative artificial intelligence design. Science, 30 April 2026. "no known free-living organism uses an alphabet of fewer than 20 amino acids. This raises a fundamental question: Can a viable cell be constructed with a reduced amino acid alphabet?" A statement against Cockell: "Computational protein modeling also indicates that as few as 9 to 12 amino acids could, in principle, encode all protein folds."
