Codon synonyms

L. Duret, Evolution of synonymous codon usage in metazoans. Curr. Opirt Genet Dev. 12, 640-649 (2002). 

As the genetic code provides 4 = 64 codons for the 20 amino acids, there are several synonymous codons for most amino acids— the code is degenerate. Three triplets do not code for amino acids, but instead signal the end of translation (stop codons). Another special codon, the start codon, marks the start of translation. The code shown here is almost universally applicable only the mitochondria (see p. 210) and a few microorganisms deviate from it slightly. 

There are 64 possible triplet codons (64 = 43 there are four choices of base at each of the three positions in a codon). However, only 61 codons are used to designate amino acids three codons are used to signal the end of the amino acid sequence for a protein, and these three codons are called termination or stop codons. With 20 amino acids used in most proteins and 61 codons to specify amino acids, some amino acids are coded for by more than one codon, i.e., there are synonymous... 

Most amino acids in proteins are specified by more than one codon (i.e. the genetic code is degenerate). Codons that specify the same amino acid (synonyms) often differ only in the third base, the wobble position, where base-pairing with the anticodon may be less stringent than for the first two positions of the codon. 

Codons that specify the same amino acid are called synonyms. Most synonyms differ only in the third base of the codon for example GUU, GUC, GUA and GUG all code for valine. During protein synthesis, each codon is recognized by a triplet of bases, called an anticodon, in a specific tRNA molecule (see Topics G10 and H2). Each base in the codon base pairs with its complementary base in the anticodon. However, the pairing of the third base of a codon is less stringent than for the first two bases (i.e. there is some wobble base-pairing ) so that in some cases a single tRNA may base-pair with more than one codon. For example, phenylalanine tRNA, which has the anticodon GAA, recognizes both of the codons UUU and UUC. The third position of the codon is therefore also called the wobble position. 

Nei and Gojobori s unweighted pathway Takes into account codon position (first, second, or third) and whether change is synonymous or nonsynonymous (unweighted version of Miyata and Yasunaga s method) 2,12... 

Four-parameter Multiplirity classes for 2-, 3-, 4-, and 6-fold degenerate codon groups are used to estimate number of synonymous substitutions per codon. Several options are available for representing constraints on amino add replacements 14... 

This can be accounted for by the wobble hypothesis it appears that when a codon in mRNA interacts with the anticodon, unconventional pairing can form between the base in the third position of the codon (3 end of triplet) and the first position of the anticodon. The unusual nucleoside inosine (Chap. 7) frequently occurs in the latter position, and it can pair with A, U, or C. The possibility of more than one type of pairing in this position accounts for the fact that when there is more than one codon for a single amino acid (called synonyms, see Table 17.1), the differences are usually in the third position only. 

It follows that the technique is useful to identify (1) point mutation (a single different nucleotide) that may be a silent mutation (also known as a synonymous mutation due to degenerate coding), resulting in a codon that codes for the same amino acid or a missense mutation (type of non-synonymous mutation) producing a codon that codes for a different amino acid the resulting protein may be non-functional but certain missense mutations can be quiet since the protein may stiU function polymorphisms, (3) insertions, and deletions. 

Figure 2 Base stacking provided by the correlations in nucleotide sequences is the major mechanism of DNA thermostability. Upper row. Real amino acid sequence and original codon bias. Middle row. The effect of codon interface is removed through the reshuffling of protein sequences while retaining the actual codons used for each amino acid. Bottom row. Codon bias in natural protein sequences is removed by using synonymous codons with equal probabilities. ApG and CpT pairs in the sense strand and ApG pairs in the antisense strand of DNA are underlined if they are located inside one codon. For example (upper row), the first ApG pair in the sense strand is in the Lys codon, whereas the second ApG pair is on the border between the codons of Leu and Val.

Codons that specify the same amino acid are called synonyms. For example, CAU and CAC are synonyms for histidine. 

Note that synonyms are not distributed haphazardly throughout the genetic code (depicted in Table 5,4). An amino acid specified by two or more synonyms occupies a single box (unless it is specified by more than four synonyms). The amino acids in a box are specified by codons that have the same first two bases but differ in the third base, as exemplified by GUU, GUC, GUA, and GUG. Thus, most synonyms differ only in the last base of the triplet. Inspection of the code shows that XYC and XYU always encode the same amino acid, whereas XYG and XYA usually encode the same amino acid. The structural basis for these equivalences of codons will become evident when we consider the nature of the anticodons of tRNA molecules (Section 29.3.9). 

Valuable synonyms. Proteins generally have low contents of Met and Trp, intermediate ones of His and Cys, and high ones of Leu and Ser. What is the relation between the number of codons of an amino acid and its frequency of occurrence in proteins What might be the selective advantage of this relation ... 

Fig. 9. Shown are the probabilities of a given codon mutating in a synonymous (open), conservative (hatched), and nonconservative (filled) way in one round of replication under error-prone conditions. The codons are grouped by the amino acid encoded, and the amino acids are grouped by category.

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