Glutamate codons

Sickle cell disease is caused by a mutation that results in the substitution of a valine residue for a glutamate residue in the sixth position of the hemoglobin P-chain. This results from the substitution of a T for an A in the glutamate codon. When (1) DNA from a patient... 

This reaction changes a glutamate codon (C-A-A) to a stop codon (U-A-A) at position C6666... 

Sickle cell anemia (MIM 141900) Sequence of codon 6 of the p chain changed from GAG in the normal gene to GTG in the sickle cell gene, resulting in substitution of valine for glutamic acid... 

RFLP analysis of the p-globin gene for genetic testing has been replaced, by PCR In combination with ASO probes on dot blots. The blot shown here corresponds to the family whose pedigree is shown in Figure T7-9. In the mutant allele, glutamate (E) at codon 6 is replaced by valine (V). 

Basis of the Sickle-Cell Mutation Sickle-cell hemoglobin has a Val residue at position 6 of the j3-globin chain, instead of the Glu residue found in normal hemoglobin A. Can you predict what change took place in the DNA codon for glutamate to account for replacement of the Glu residue by Val ... 

Table 27.4 in the text lists the messenger RNA codons for the various amino acids. The codons for valine and for glutamic acid are ... 

As can be seen, the codons for glutamic acid (GAA and GAG) are very similar to two of the codons (GUA and GUG) for valine. Replacement of adenine in the glutamic acid codons by uracil causes valine to be incorporated into hemoglobin instead of glutamic acid and is responsible for the sickle cell trait. 

The genetic code is not universal but is the same in most organisms. Exceptions are found in mitochondrial genomes where some codons specify different amino acids to that normally encoded by nuclear genes. In mitochondria, the UGA codon does not specify termination of translation but instead encodes for tryptophan. Similarly, in certain protozoa UAA and UAG encode glutamic acid instead of acting as termination codons. 

Figure 5.8 An hypothetical genetic code in which aspartic acid and glutamic acid are coded for by twice the number of codons that exist in the natural code, thus producing a world of more acidic proteins.

One kind of RNA—called, fittingly, messenger RNA—carries a message to the ribosome, where protein synthesis actually takes place. At the ribosome, messenger RNA calls up a series of transport RNA molecules, each of which is loaded with a particular amino acid. The order in which the transport RNA molecules are called up—the sequence in which the amino acids are built into the protein chain—depends upon the sequence of bases along the messenger RNA chain. Thus, GAU is the code for aspartic acid UUU, phenylalanine GUG, valine. There are 64 three-letter code words codons) and only 20-odd amino acids, so that more than one codon can call up the same amino acids CUU and CUC, leucine GXA and GAG, glutamic acid. 

---