Genetic code variations

Fig. 1.5 Schematic representation of the evolution of life from its precursors, on the basis of the definition of life given by the authors. If bioenergetic mechanisms have developed via autonomous systems, the thermodynamic basis for the beginning of the archiving of information, and thus for a one-polymer world such as the RNA world , has been set up. Several models for this transition have been discussed. This phase of development is possibly the starting point for the process of Darwinian evolution (with reproduction, variation and heredity), but still without any separation between genotype and phenotype. According to the authors definition, life begins in exactly that moment when the genetic code comes into play, i.e., in the transition from a one-polymer world to a two-polymer world . The last phase, open-ended evolution, then follows. After Ruiz-Mirazo et al. (2004)...

Exceptions That Prove the Rule Natural Variations In the Genetic Code... 

One would expect little room for variation in the genetic code. Even a single amino acid substitution can have profoundly deleterious effects on the structure of a protein. Nevertheless, variations in the code do occur in some organisms, and they are both interesting and instructive. The types of variation and their rarity provide powerful evidence for a common evolutionary origin of all living things. 

Of the very few variations in the genetic code that we know of, most occur in mitochondrial DNA (mtDNA), which encodes only 10 to 20 proteins. Mitochondria have their own tRNAs, so their code variations do not affect the much larger cellular genome. 

These variations tell us that the code is not quite as universal as once believed, but that its flexibility is severely constrained. The variations are obviously derivatives of the normal code, and no example of a completely different code has been found. The limited scope of code variants strengthens the principle that all life on this planet evolved on the basis of a single (slightly flexible) genetic code. 

Suppressor tRNAs constitute an experimentally induced variation in the genetic code to allow the reading of what are usually termination codons, much like the naturally occurring code variations described in Box 27-2. Nonsense suppression does not completely disrupt normal information transfer in a cell, because the cell usually has several copies of each tRNA gene some of these duplicate genes are weakly expressed and account for only a minor part of the cellular pool of a particular tRNA. Suppressor mutations usually involve a minor tRNA, leaving the major tRNA to read its codon normally. 

The mutation that leads to creation of a suppressor tRNA does not always occur in the anticodon. The suppression of UGA nonsense codons generally involves the tRNATlp that normally recognizes UGG. The alteration that allows it to read UGA (and insert Trp residues at these positions) is a G to A change at position 24 (in an arm of the tRNA somewhat removed from the anticodon) this tRNA can now recognize both UGG and UGA. A similar change is found in tRNAs involved in the most common naturally occurring variation in the genetic code (UGA = Trp see Box 27-2). 

Many of the known variations in the genetic code are found in genes of mitochondria and chloroplasts. It is easy to see why these genetic systems might be more plastic, since they frequently encode only 10-20 proteins. The remainder of the organellar proteins are derived by importing nuclear gene products. 

Natural variation in the genes that encode adrenergic receptors (ARs) have been identified. The variations of major interest for common diseases are those that occur with allele frequencies >1% and are termed polymorphisms. Within the coding region, polymorphic variation can result in either a change in the encoded amino acid (nonsynonymous) or, because of the redundancy of the genetic code, have no effect on the encoded residue (synonymous). The most common variants are single nucleotide polymorphisms (SNPs), but insertions and deletions are also found. AR polymorphisms have been considered as poten-... 

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