Serine codons

In the absence of an AGAC the ribosomes will prodnce the artificial polypeptides, polyphenylalanine (as specified by the codon UUU) or polyproline (as specified by the codon CCC). However, when streptomycin is added, the ribosomes prodnce a mixture of polythreonine (codon ACU) and poly serine (codon UCU). The misreading of the codons does not appear to be random U is read as A or C and C is read as A or U. If such misreading occurs in whole cells the accumulation of non-functional or toxic proteins would eventually prove fatal to the cells. There is some evidence that the bacterial cell membrane is damaged when the cells attempt to excrete the faulty proteins. 

Silent mutation The codon containing the changed base may code for the same amino acid. For example, if the serine codon UCA is given a different third base—U—to become UCU, it still codes for serine. Therefore, this is termed a "silent" mutation. 

Specific. Each codon is a signal for a specific amino acid. The majority of codons that code for the same amino acid possess similar sequences. For example, in each of the four serine codons (UCU, UCC, UCA, and UCG) the first and second bases are identical. Consequently, a point mutation in the third base of a serine codon would not be deleterious. 

As shown in Figure 45.1, the bases appear in complementary pairs, A with T and G with C in this particular example, the sequence for one strand of DNA is A-T-C-G-T- while the other strand is -T-A-G-C-A-. The sequences of the bases attached to the sugar-phosphate backbone direct the production of proteins from amino acids. Along each strand, groups of three bases, called codons, correspond to individual amino acids. For example, in Figure 45.1, the triplet CGT, acting as a codon, would correspond to the amino acid serine. One codon, TAG, indicates where synthesis should begin in the DNA strand, and other codons, such as ATT, indicate where synthesis should stop. 

The information contained in the DNA (i.e., the order of the nucleotides) is first transcribed into RNA. The messenger RNA thus formed interacts with the amino-acid-charged tRNA molecules at specific cell organelles, the ribosomes. The loading of the tRNA with the necessary amino acids is carried out with the help of aminoacyl-tRNA synthetases (see Sect. 5.3.2). Each separate amino acid has its own tRNA species, i.e., there must be at least 20 different tRNA molecules in the cells. The tRNAs contain a nucleotide triplet (the anticodon), which interacts with the codon of the mRNA in a Watson-Crick manner. It is clear from the genetic code that the different amino acids have different numbers of codons thus, serine, leucine and arginine each have 6 codewords, while methionine and tryptophan are defined by only one single nucleotide triplet. 

The myopathic form of CPT deficiency is due to a defect of CPT II. The gene for CPT II has been localized to chromosome 1, and several mutations have been identified in patients [4]. As in the case of McArdle s disease (see above), one mutation, a serine-to-leucine substitution at codon 113, is far more common than the others in Caucasians and can be screened for in genomic DNA from blood cells, thus potentially avoiding muscle biopsy. 

Figure 3.11. Structure of FcyRIIIA and FcyRIIIB. In FcyRIIIA, residue 203 is phenylalanine (Phe), which is followed by a hydrophobic transmembrane domain and a cytoplasmic domain. In FcyRIIIB, residue 203 is serine (Ser), which is followed by a stop codon. See text for details.

Kawaguchi, Y., Honda, H., Taniguchi-Morimura, . and Iwasaki, S., The codon CUG is read as serine in an asporogenic yeast Candida cyUndracea Nature, 1989, 341, 164-166. 

In the next step, translation, the sequence of nucleotides in the newly synthesized mRNA strand is used to determine the sequence of amino acids in the protein to be synthesized. This is done by way of a genetic code, which was fully deciphered by 1966 and is shown in Figure 13.34. According to the genetic code, it takes three mRNA nucleotides—each three-nucleotide unit is called a codon—to code for a single amino acid. The mRNA nucleotide sequence AGU, for example, codes for the amino acid serine, and AAG codes for lysine. (Note from Figure 13.34 that more than one codon can call for the same amino acid.) A few codons, such as AUG and UGA, are the signals for protein synthesis to either start or stop. 

Another important technique was based on the observation that synthetic trinucleotides induced the binding to ribosomes of tRNA molecules that were "charged" with their specific amino acids 38/39 For example, the trinucleotides UpUpU and ApApA stimulated the binding to ribosomes of 14C-labeled phenylalanyl-tRNA and lysyl-tRNA, respectively. The corresponding dinucleotides had no effect, an observation that not only verified the two codons but also provided direct evidence for the triplet nature of the genetic code. Another powerful approach was the use of artificial RNA polymers, synthesized by combined chemical and enzymatic approaches.40 For example, the polynucleotide CUCUCUCUCU led to the synthesis by ribosomes of a regular alternating polypeptide of leucine and serine. 

Figure 14.8 The original scheme for oligodeoxynucleotide-directed mutagenesis. The mismatched primer is designed to mutate the codon for cysteine (TGC) to that for serine (AGC).

It is quite certain that the code involves a particular sequence of three nucleotides for each amino acid. Thus the sequence A-A-A codes for lysine, and U-C-G codes for serine. The sequences or codons for all twenty amino acids are known. 

A single tRNA can insert serine in response to three different codons UCC, UCU, or UCA. What is the anticodon sequence of this tRNA ... 

Garey, J.R. and Wolstenholme, D.R. (1 989) PlatyheIminth mitochondrial DNA evidence for early evolutionary origin of a tRNA(ser AGN) that contains a dihydrouridine arm replacement loop, and of serine-specifying AGA and AGG codons. Journal of Molecular Evolution 28, 374-387. 

The sequence of bases (A, G, T, and C) in a strand of DNA specifies the order in which amino acids are assembled to form proteins. The genetic code is the collection of base sequences that correspond to each amino acid, codon. Since there are only four bases in DNA and twenty amino acids in protein, each codon must contain at least three bases.5 Two bases cannot serve as codons because there are only 42 possible pairs of four bases, but three bases can serve because there are 43 = 64 possible triplets. Since the number of possible triplets are more than enough, several codons designate the same ammo acid. In other words, the genetic code is highly redundant as shown in Table 7.1. For example, UCU, UCC, UCA, UCG, AGU, and AGC are all codes for serine. 

But perhaps the discovery that caused the greatest surprise was the presence of these substituted adenine derivatives in the anti-codon loops of several transfer RNAs—not only in plant tRNAs but in those for serine and tyrosine in yeast (Bergquist and Matthews, 1962) in E. coli and probably in all other organisms. 

Table 6.1 shows the relationship between the codon sequence in mRNA and its corresponding amino acid in the new protein. Because there are 64 (43) different anticodon combinations and only 20 encoded amino acids, some different anticodon sequences encode for the same amino acid. Generally, all the anticodons matching a given amino acid will have the same first two nucleotides. Exceptions are arginine, serine, and isoleucine. For example, the codon for proline will always start with CC, but the arginine codon may start with either AG or CG. The 3 end of the tRNA anticodon pairs with the 5 end of the mRNA codon. In other words, the codon and anticodon align and bind in an antiparallel fashion. 

The element Se—not really a metal—is known to play a key role in enzymes such as the well-known glutathione peroxidase, formate dehydrogenase, glycine reductase, and the previously mentioned hydrogenases (Chapter 9). The unusual amino acid selenocysteine has a unique codon on the DNA (TGA/UGA), but selenation of serine also appears to be possible [16]. A brief review on Selenium can be found in the literature [17],... 

Another widely studied apo A-IV SNP is an A—>T polymorphism at nucleotide 2346 (first base of codon 347), which causes a threonine-to-serine substitution in the protein product.54-55 The A—>T variant at codon 347 occurs at almost double the frequency of the 360G—>T variant with a prevalence of 22% in Caucasian populations.55-56 However, ethnic differences have been described with lower frequencies in African blacks (9.5%) and Hispanic populations (12.9%).53 The 360G— T and 347A—>T genetic variants are in strong linkage disequilibrium and tend not to occur together.55-57... 

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