The structural basis of the genetic code: amino acid recognition by aminoacyl-tRNA synthetases 28 July 2020 1
One of the most profound open questions in biology is how the genetic code was established. While proteins are encoded by nucleic acid blueprints, decoding this information in turn requires proteins. The emergence of this self-referencing system poses a chicken-or-egg dilemma and its origin is still heavily debated. Aminoacyl-tRNA synthetases (aaRSs) implement the correct assignment of amino acids to their codons and are thus inherently connected to the emergence of genetic coding. These enzymes link tRNA molecules with their amino acid cargo and are consequently vital for protein biosynthesis. Beside the correct recognition of tRNA features, highly specific non-covalent interactions in the binding sites of aaRSs are required to correctly detect the designated amino acid and to prevent errors in biosynthesis. The minimization of such errors represents the utmost barrier for the development of biological complexity and accurate specification of aaRS binding sites is proposed to be one of the major determinants for the closure of the genetic code. Beside binding side features, recognition fidelity is controlled by the ratio of concentrations of aaRSs and cognate tRNA molecules and may involve spatial secondary structures motifs in addition to side chain configurations.
The evolutionary origin of aaRSs is hard to track. Phylogenetic analyses of aaRS sequences show that they do not follow the standard model of life; the development of aaRSs was nearly complete before the Last Universal Common Ancestor (LUCA).
My comment: Since the set of aminoacyl tRNA synthetases had to be fully set up and operational prior life started, they could not have been the product of evolutionary pressures.
aaRSs can be divided into two distinct classes (Class I and Class II) that share no similarities at sequence or structure level.
Storage and directed transfer of information is the key requirement for the development of life. Yet any information stored on our genes is useless without its correct interpretation.
My comment: There are many different activities involved with interpretation 2, and they are ALWAYS performed by an intelligent agency. In our daily experience, human intelligence. There is no known ability known by non-intelligent action, being able to perform it. In life, this action is key. The correct translation of the message stored in mRNA is essential for all life forms. Materialists agree and acknowledge, that science has not discovered yet how the cipher, or translation of the triplet codons to amino acids emerged, but that, in principle, a non-intelligent mechanism can be discovered. How, if the interpretation of a message requires the beforehand agreement of meaning of the language? I think that this child is born already dead.
The genetic code defines the ruleset to decode this information.
My comment: Establishing a rule is also unambiguously, always, the action of intelligence.
Aminoacyl-tRNA synthetases are at the heart of this process. We extensively characterize how these enzymes distinguish all natural amino acids based on the computational analysis of crystallographic structure data.
My comment: Making distinctions also requires mental activity and is always observed to be the action of intelligence. 4
The results of this meta-analysis show that the correct read-out of genetic information is a delicate interplay between the composition of the binding site, non-covalent interactions, error correction mechanisms, and steric effects.
My comment: As I have investigated, there are no less than eleven error checks and repair mechanisms in operation in translation. 5 A delicate interplay means that the individual players have only function once they operate in an orchestrated fashion in a conjoined manner. It is not feasible to think that the individual enzymes, subunits, scaffold proteins, chaperone's and co-factors involved in the synthesis of the players in translation operation could emerge prebiotically, and unguided if individually, they bear no function whatsoever. This is not an argument from incredulity but based on our knowledge of the range of capability of what unguided random chaotic events can do. They do not complexify but randomize molecules.
One of the most profound open questions in biology is how the genetic code was established. While proteins are encoded by nucleic acid blueprints, decoding this information in turn requires proteins. The emergence of this self-referencing system poses a chicken-or-egg dilemma and its origin is still heavily debated
My comment: This is of course sound in my ears, and exposes precisely the problem that we, creationists, have been outlining all along. There are several chicken and egg problems in regards to biochemical systems required to kick-start life, without any solution whatsoever in sight.
Aminoacyl-tRNA synthetases (aaRSs) implement the correct assignment of amino acids to their codons and are thus inherently connected to the emergence of genetic coding. These enzymes link tRNA molecules with their amino acid cargo and are consequently vital for protein biosynthesis.
My comment: As such, Aminoacyl-tRNA synthetases (aaRSs) are vital for life and its emergence itself.
Beside the correct recognition of tRNA features, highly specific non-covalent interactions in the binding sites of aaRSs are required to correctly detect the designated amino acid and to prevent errors in biosynthesis.
My comment: How could that correct recognition have emerged, if a false detection and recognition results in error biosynthesis? That indicates the ability of the correct recognition had to be fully right and operational right from the beginning.
The minimization of such errors represents the utmost barrier for the development of biological complexity and accurate specification of aaRS binding sites is proposed to be one of the major determinants for the closure of the genetic code
My comment: This adds further difficulty for proponents of materialistic scenarios: The error check and repair mechanisms had to be fully in place as well right from the start, or the mutation and error rate would be far too high, and the system would never be able to get "off the hook".
The evolutionary origin of aaRSs is hard to track.
My comment: Not only is the origin of Aminoacyl-tRNA synthetases hard to track. Evolution is not even an adequate mechanism to explain its origin, because evolution depends on molecular machines, that are synthesized by the very process in which Aminoacyl-tRNA synthetases are involved. So the only alternative to design is random unguided prebiotic events.
The development of aaRSs was nearly complete before the Last Universal Common Ancestor (LUCA)
My comment: Thanks to the authors for confirming my point. The emergence of those is an abiogenesis problem, and not a problem of evolution.
Their complex evolutionary history included horizontal gene transfer, fusion, duplication, and recombination events
My comment: This is a pseudo-scientific claim. A shameless assertion without any basis in observation whatsoever.
Sequence analyses and subsequent structure investigations revealed that aaRSs can be divided into two distinct classes (Class I and Class II) that share no similarities at sequence or structure level. Each of the classes is responsible for 10 of the 20 proteinogenic amino acids and can be further grouped into subclasses
My comment: Even, let's suppose that evolutionary mechanisms would play a role, why should or would horizontal gene transfer, fusion, duplication, and recombination events result in the making of such complex proteins, if they bear only function in joint cooperation with tRNA's, and the ribosome, and the existence of the amino acid alphabet, which they are made for to select during the polypeptide elongation process?
Origin of genetic coding
One theory, ambiguity reduction of physicochemical properties, considers the major selective pressure for genetic code emergence to be the minimization of deleterious effects of mutations.
My comment: This is pseudo-scientific nonsensical just so story-telling and wishful thinking. There was no selection in operation prebiotically. Molecules lying around had no urge to minimize mutations of whatever the author hypothesizes.
In order to fulfill their biological function aaRSs are required to catalyze two distinct reaction steps. Prior to its covalent attachment to the 3’ end of the tRNA molecule, the designated amino acid is activated with adenosine triphosphate (ATP) and an aminoacyl-adenylate intermediate is formed.
My comment: That means, a steady supply of ATP molecules is required right from the beginning in order for the protein to bear function, and if one of the two reaction steps is missing, no deal either. This is an all or nothing situation. The molecule had to be able to perform BOTH functions, and have a steady supply of ATP, or no deal, translation would not be possible, and life as we know it, could not exist either.
(i) Class I and Class II aaRSs employ different overall strategies for amino acid recognition.
My comment: Developing strategies require a strategist. And recognition, and intelligent agency that can implement the autonomous ability of recognition.
Interaction patterns and binding site composition are the most important drivers to mediate specificity. The analysis of interaction fingerprints suggests that error-free recognition is a delicate task demanding a complex interplay between binding site composition, interaction patterns, editing mechanisms, and steric effects.
My comment: Both, these interaction patterns, and binding site composition, are very specific, and only work once fully specified. How did the formation of the correct interaction pattern occur? How could it emerge by unguided events? Trial and error? What about the editing mechanisms? Editing requires the ability of error detection and repair. This is by no means an easy task and requires foresight.
To execute genetic coding rules aaRSs must recognize both amino acids and tRNAs with high specificity—a process we call assignment catalysis—so that the latter can escort the former to the ribosome for protein synthesis.
Last edited by Otangelo on Thu 31 Dec 2020 - 15:08; edited 1 time in total