The genetic code is degenerate i.e. more than one codon can code for a single amino acid. Due to this, of the 64 codons, 61 codons code for. A correlation of gene expression level with synonymous codon or amino acid abundant and low-cost production of the amino acid, creating a large market. The specific properties of the code, e.g. that similar amino acids tend to have similar codons assigned , inspired many scientists to formulate.
There is supposedly no stereochemical connection between codons and the amino acids they encode; such a connection should be expected for any form of secondary or higher structural information transfer. It has been carefully analyzed, and rejected, by many scientists including Woese [ 24 ].
Protein synthesis from a nucleic acid template is a series of enzyme reactions, and enzyme reactions are reversible at least in theory.
Therefore it is to be expected that even the enzyme reactions involved in translation should be at least in theory reversible. As a consequence, translation as whole should be reversible, even if the process is very complex and complicated. All natural material processes and there are no others follow the second law of thermodynamics, which entails the successive breakdown of order and replacement by disorder and heat.
The only known natural process that might appear to be an exception is Life, which periodically shows signs of negative entropy, creation of order from disorder.
Mathematics, an extremely abstract, non-experimental science, makes a very clear distinction between proof and conjecture. For one thing, it is not completely wrong: Proteins have long been regarded as the carriers of important biological including genetic information since beforeand many scientists still feel it necessary to state this every day, completely forgetting that inherited information is not the only biologically important type of information.
However, this statement acquired a basis somewhat later, inwhen Anfinsen et al. This suggested and seemed to confirm that all the information required for a protein to adopt its final conformation is encoded in its primary structure.
Objections to the Dogma There are three categories of objection against the Dogma: Formal, Conceptual and Experimental. There is a formal mistake in the presentation of the Dogma.
Information transfer between macromolecules has two different, readily distinguished forms. The first category is physical transfer or transformation of information from one sequence to another, as in transcription and translation. The second category is the recognition type of information transfer, such as specific binding recognition between complementary nucleic acid sequences.
Specific interactions between proteins and nucleic acids for example transcription factor binding to promoters or enhancers, or restriction enzyme binding to cut-sites also belong to this category, as do specific protein-protein interactions such as receptor—ligand and antigen—antibody interactions. Much criticism was directed against the Dogma because there was disagreement about the existence of recognition-type information transfer between proteins or between proteins and nucleic acids [ 30 ].
Figure 2 clarifies this situation.
Evolution of the Genetic Code Ã¢Â€Â“ Some Novel Aspects
Biological information flow transformation and recognition between nucleic acids and proteins. Transcription and translation are indicated by black arrows, while the red arrows indicate the theoretical but not observed possibility of reverse translation. Information transfer through macromolecular interactions is indicated by blue arrows.
There are many unanswered questions. Some parts of the Dogma have become scientifically obsolete because of direct experimental evidence: One crucial statement of the Dogma, the prohibition of any kind of direct information transfer from proteins, is still neither confirmed nor refuted by direct laboratory experiments. Information here means the precise determination of sequence, either of bases in the nucleic acid or of amino acid residues in the protein.
The essence of the statement is that a proteins fold spontaneously amino acid sequences contain all the information necessary for folding - no additional information is required ; b transfer of folding 3D information from proteins to nucleic acid sequences 1D is not possible because they are too markedly different! In addition, there are the following points. This is also indirect evidence for the possibility and the real existence of stereochemically-specific interactions between codons and their encoded amino acids.
This observation is the basis of the Proteomic Code and explains how specific 3D protein information is encoded in a 1D nucleic acid sequence. This observation further confirms the importance and non-randomness of wobble bases. In other words, the genetic code 64 codons is redundant in respect of encoding the 20 amino acids, but the excess codon information is used to store and encode specific protein configurations and protein-protein interactions.
This observation, together with the concept of the Proteomic Code, led us to formulate the hypothesis of nucleic acidassisted protein folding [ 39 ]. None of these observations directly or indirectly indicates the existence of transcription-like transfer of biological information from proteins to nucleic acids or to other proteins.
However, it has become clear that there is no conceptual hindrance to such kinds of information transfer. Storage and transfer of 3D structural information is possible in nucleic acids in addition to the storage and transfer of amino acid sequence coding information described by Nirenberg. In this case the information in the nucleic acids corresponds to that in the proteins, but the nucleic acids and proteins, the carriers of that information, are not connected to each other by rules such as the Genetic Code.
Prions [ 31 ], proteinaceous and infectious pathogens, cause a group of invariably fatal neurodegenerative diseases: The prion gene, PrNP [ 41 ], is normally present in the genomes of many species and is expressed predominantly in the nervous system in mammals. It can be converted into a modified protein PrPSc through a post-translational process.
PrPSc has a strong tendency to aggregate into amyloid-like material, which is biologically undegradable. Two hypotheses might serve to explain this reaction: It is important to note that these nucleation and catalyzed-conversion hypotheses are not mutually exclusive. Whatever the action of PrPSc, this molecule represents a molecular phenotype that is normally represented in the genome no differently from normal PrPC.
The PrPSc phenotype cannot be inherited because it kills cells merely by its presence. However, this protein-induced self-perpetuating mechanism becomes very interesting in situations where the structural variant Pv, corresponding to PrPSc of a naturally occurring protein Pn, corresponding to PrPC provides benefits for the cells that carry it.
amino acid codons: Topics by francinebavay.info
The Pv phenotype becomes inherited by the simple mechanical segregation of cytoplasmic proteins, without the involvement of a specific genotype or the complex expression of this particular phenotype via transcription and translation. This entirely protein-based virtual inheritance might go on for an unlimited number of generations Figure 3.
Prions and protein-mediated epigenetic inheritance. An abnormally-folded variant PrPSc appears in the cells under pathological conditions. It also aggregates into amyloid, which forms undegradable deposits, degenerates and kills the cells c. It is theorized that, after several generations, mutation and natural selection might provide a genetically inherited variant Pvx of Pv encoded by the Pvx genewhich replaces the original Pv and its functions f.
There are numerous examples of this protein-based inheritance from yeast prions [ 46 ]. If and when that happens, the phenotypic information is formally transferred reverse-translated? However, it might be difficult for some scientists to see this as an example of reverse translation, or reverse transfer of biological information from proteins to nucleic acids.
Recent Status of Reverse Translation Historically, speculations have been published that poly-amino acid reverse translation PAA-RT may have existed in nature in prebiotic evolution and could exist undiscovered in nature today [ 50 - 54 ]. There are several patents relating to this notion.
Their common feature is an attempt to arrange codon-amino acid complexes along a template peptide sequence, polymerize the codon parts, and use the product as the nucleic acid template for synthesis of DNA and of proteins that are similar or identical to the template protein [ 5556 ]. One product under development is called PeplicaTM [ 57 ]. After the reverse translation step, the resulting nucleic acid is amplified by a conventional amplification method such as PCR.
Using the amplification product, the identity of the protein can be determined and, if desired, more of it can be produced.
In principle, PeplicaTM could be used to detect as little as one copy of a protein molecule. The differences between genome and proteome are of course well recognized, as is the importance of epigenetic modifications of proteins. The example of prions raises a very intriguing question: It might be necessary in future to consider sequencing proteomes, just as genomes have been sequenced recently. The development of bioinformatics, sequence databases and computational tools also offer exceptionally effective approaches to reviewing and further developing classical statements in molecular biology [ 58 - 62 ].
Larger proteins cannot fold correctly without the assistance of other proteins, called chaperons. Most recently-identified chaperons are themselves proteins, which are also produced by equally information-losing translations, so they may also need chaperones for their own folding.
Thus, the information deficit in proteins potentially leads to a process of infinite regression. The concept of the Proteomic Code gives a relatively simple explanation of the storage and transfer of folding information in nucleic acids using the excess redundant amino acid coding information.
The Proteomic Code means that co-locating amino acids are preferentially encoded by partially complementary codons [ 63 ] Figure 4. Coding of folding by synonymous codon usage. Two amino acids may be coded by partially complementary or non-complementary codons. This structural code the Proteomic Code determines whether the coded amino acids will preferentially co-locate or separate in a translated protein.
Similarly, separated amino acids are preferentially encoded by noncomplementary synonymous codons. The Proteomic Code indicates the action of a statistical rule: By extension, this means that the peptide structure is represented, at least to some degree, in mRNA structure Figure 5.
Effect of synonymous codons on the folding structure of mRNA and coded peptides. A peptide consists of 6R positively charged, red and 6E negatively charged, blue amino acid residues. It contains reactive termini that interact with each other. This peptide has many equally possible and favored configurations tertiary structure and several copies might interact with each other quaternary structurefor example a compact, globular, configuration that forms dimers a.
This structural information can be transferred into the peptide during translation and defines different 3D structures and interactions b, c. Structurally coded parts of sequences are shaded grey.
What is the biological significance of the extensive degeneracy of the genetic code? If the code were not degenerate, 20 codons would designate amino acids and 44 would lead to chain termination.
The probability of mutating to chain termination would therefore be much higher with a nondegenerate code. Chain-termination mutations usually lead to inactive proteins, whereas substitutions of one amino acid for another are usually rather harmless.
Thus, degeneracy minimizes the deleterious effects of mutations. Degeneracy of the code may also be significant in permitting DNA base composition to vary over a wide range without altering the amino acid sequence of the proteins encoded by the DNA.
How is mRNA interpreted by the translation apparatus? These codons are read not by tRNA molecules but rather by specific proteins called release factors Section Binding of the release factors to the ribosomes releases the newly synthesized protein.
The start signal for protein synthesis is more complex. Polypeptide chains in bacteria start with a modified amino acid—namely, formylmethionine fMet. However, AUG is also the codon for an internal methio-nine residue, and GUG is the codon for an internal valine residue. Hence, the signal for the first amino acid in a prokaryotic polypeptide chain must be more complex than that for all subsequent ones. In bacteria, the initiating AUG or GUG codon is preceded several nucleotides away by a purine-rich sequence that base-pairs with a complementary sequence in a ribosomal RNA molecule Section Once the initiator AUG is located, the reading frame is established—groups of three nonoverlapping nucleotides are defined, beginning with the initiator AUG codon.
Initiation of Protein Synthesis. Start signals are required for the initiation of protein synthesis in A prokaryotes and B eukaryotes.
The base sequences of many wild-type and mutant genes are known, as are the amino acid sequences of their encoded proteins. In each case, the nucleotide change in the gene and the amino acid change in the protein are as predicted by the genetic code.
Furthermore, mRNAs can be correctly translated by the proteinsynthesizing machinery of very different species. For example, human hemoglobin mRNA is correctly translated by a wheat germ extract, and bacteria efficiently express recombinant DNA molecules encoding human proteins such as insulin. These experimental findings strongly suggested that the genetic code is universal. A surprise was encountered when the sequence of human mitochondrial DNA became known.
Human mitochondria read UGA as a codon for tryptophan rather than as a stop signal Table 5. Mitochondria of other species, such as those of yeast, also have genetic codes that differ slightly from the standard one. The genetic code of mitochondria can differ from that of the rest of the cell because mitochondrial DNA encodes a distinct set of tRNAs.
Do any cellular protein-synthesizing systems deviate from the standard genetic code? Thus, the genetic code is nearly but not absolutely universal. Variations clearly exist in mitochondria and in species, such as ciliates, that branched off very early in eukaryotic evolution. It is interesting to note that two of the codon reassignments in human mitochondria diminish the information content of the third base of the triplet e.