Aminoacyl-tRNA synthetases point to design
https://reasonandscience.catsboard.com/t2280-aminoacyl-trna-synthetases
The synthetases have several active sites that enable them to:
(1) recognize a specific amino acid,
(2) recognize a specific corresponding tRNA(with a specific anticodon),
(3) react the amino acid with ATP (adenosine triphosphate) to form an AMP (adenosine monophosphate) derivative, and then, finally,
(4) link the specific tRNA molecule in question to its corresponding amino acid. Current research suggests that the synthetases recognize particular three-dimensional or chemical features (such as methylated bases) of the tRNA molecule. In virtue of the specificity of the features they must recognize, individual synthetases have highly distinctive shapes that
derive from specifically arranged amino-acid sequences. In other words, the synthetases are themselves marvels of specificity.37
The accuracy of translation depends directly on the specificity of associations between tRNAs and tRNA-binding proteins called aminoacyl-tRNA synthetases (aaRSs). In general, to each type of encoded amino acid corresponds multiple tRNA isoacceptors and a unique aaRS that covalently attaches (aminoacylates or “charges”) that type of amino acid to the ends of those tRNAs at their acceptor stems in an ATP-dependent two-step reaction for later delivery to the A-site of the ribosome for codon-directed insertion of amino acids into growing peptide chains. The tRNAs and aaRSs associated to the same amino acid type are called cognate pairs 1
The original evolutionary stages of the aaRS–tRNA network remain relatively obscure.
My comment: That is a grotesque understatement. There is no reasonable explanation whatsoever of how this amazing molecular machinery and assembly factory could have emerged. Why the author mentions evolution is misleading, in face of the fact that this whole process had to emerge prior to DNA replication, and as such, evolution could not have been in play yet.
Signature in the cell, page 427
There is a difficulty associated with generating the enzymatic capacities of synthetases in an RNA world. The probability of ribozymes arising with even the limited capacity to catalyze aminoacyl bonds is very small. The first researchers who found an RNA molecule capable of self-aminoacylation with phenylalanine had to sift through a preengineered pool of 170 trillion (or 1.7 × 10^14) RNA molecules (see Illangasekare, et al., “Aminoacyl-RNA Synthesis Catalyzed by an RNA”). This suggests that the probability of finding a single RNA molecules that could catalyze the formation of this bond is roughly one chance in 1014. But to generate an RNA-based genetic code equivalent to that in the modern translation system would require not just one such ribozyme, but nineteen others (corresponding to each aminoacyl-tRNA synthetase enzyme) working together as a system, each with its own specific role. And that would require sequestering all the components of the system in a compartment that prevents interference from useless RNAs. If the other necessary ribozymes were roughly as rare as the first, then the probability of sequestering one additional ribozyme that performs the same function with a different amino acid would be the square of the original probability, or less than chance 1 in 1028. The probability of sequestering three such ribozymes in close quarters would be the cube of that initial probability, or less than one chance in 1042. The probability of sequestering twenty such ribozymes in close enough proximity to function as a system—as a part of a genetic code—would be prohibitively small, no better than 1 chance in 10^280. Overcoming these odds would require a huge infusion of information (930 bits). And still these ribozymes would not be capable of coordinating the complex two-stage reaction that actual synthetase enzymes perform in extant cells.
1. https://www.sciencedirect.com/science/article/pii/S0040580918300789
https://reasonandscience.catsboard.com/t2280-aminoacyl-trna-synthetases
The synthetases have several active sites that enable them to:
(1) recognize a specific amino acid,
(2) recognize a specific corresponding tRNA(with a specific anticodon),
(3) react the amino acid with ATP (adenosine triphosphate) to form an AMP (adenosine monophosphate) derivative, and then, finally,
(4) link the specific tRNA molecule in question to its corresponding amino acid. Current research suggests that the synthetases recognize particular three-dimensional or chemical features (such as methylated bases) of the tRNA molecule. In virtue of the specificity of the features they must recognize, individual synthetases have highly distinctive shapes that
derive from specifically arranged amino-acid sequences. In other words, the synthetases are themselves marvels of specificity.37
The accuracy of translation depends directly on the specificity of associations between tRNAs and tRNA-binding proteins called aminoacyl-tRNA synthetases (aaRSs). In general, to each type of encoded amino acid corresponds multiple tRNA isoacceptors and a unique aaRS that covalently attaches (aminoacylates or “charges”) that type of amino acid to the ends of those tRNAs at their acceptor stems in an ATP-dependent two-step reaction for later delivery to the A-site of the ribosome for codon-directed insertion of amino acids into growing peptide chains. The tRNAs and aaRSs associated to the same amino acid type are called cognate pairs 1
The original evolutionary stages of the aaRS–tRNA network remain relatively obscure.
My comment: That is a grotesque understatement. There is no reasonable explanation whatsoever of how this amazing molecular machinery and assembly factory could have emerged. Why the author mentions evolution is misleading, in face of the fact that this whole process had to emerge prior to DNA replication, and as such, evolution could not have been in play yet.
Signature in the cell, page 427
There is a difficulty associated with generating the enzymatic capacities of synthetases in an RNA world. The probability of ribozymes arising with even the limited capacity to catalyze aminoacyl bonds is very small. The first researchers who found an RNA molecule capable of self-aminoacylation with phenylalanine had to sift through a preengineered pool of 170 trillion (or 1.7 × 10^14) RNA molecules (see Illangasekare, et al., “Aminoacyl-RNA Synthesis Catalyzed by an RNA”). This suggests that the probability of finding a single RNA molecules that could catalyze the formation of this bond is roughly one chance in 1014. But to generate an RNA-based genetic code equivalent to that in the modern translation system would require not just one such ribozyme, but nineteen others (corresponding to each aminoacyl-tRNA synthetase enzyme) working together as a system, each with its own specific role. And that would require sequestering all the components of the system in a compartment that prevents interference from useless RNAs. If the other necessary ribozymes were roughly as rare as the first, then the probability of sequestering one additional ribozyme that performs the same function with a different amino acid would be the square of the original probability, or less than chance 1 in 1028. The probability of sequestering three such ribozymes in close quarters would be the cube of that initial probability, or less than one chance in 1042. The probability of sequestering twenty such ribozymes in close enough proximity to function as a system—as a part of a genetic code—would be prohibitively small, no better than 1 chance in 10^280. Overcoming these odds would require a huge infusion of information (930 bits). And still these ribozymes would not be capable of coordinating the complex two-stage reaction that actual synthetase enzymes perform in extant cells.
1. https://www.sciencedirect.com/science/article/pii/S0040580918300789
