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A less degenerate site would produce a nonsynonymous mutation on some of the substitutions. An example (and the only) 3-fold degenerate site is the third position of an isoleucine codon. AUU, AUC, or AUA all encode isoleucine, but AUG encodes methionine. In computation, this position is often treated as a twofold degenerate site.
Saturation mutagenesis is commonly achieved by site-directed mutagenesis PCR with a randomised codon in the primers (e.g. SeSaM) [2] or by artificial gene synthesis, with a mixture of synthesis nucleotides used at the codons to be randomised. [3] Different degenerate codons can be used to encode sets of amino acids. [1]
Point substitution mutations of a codon, classified by their impact on protein sequence. A synonymous substitution (often called a silent substitution though they are not always silent) is the evolutionary substitution of one base for another in an exon of a gene coding for a protein, such that the produced amino acid sequence is not modified.
Four novel alternative genetic codes were discovered in bacterial genomes by Shulgina and Eddy using their codon assignment software Codetta, and validated by analysis of tRNA anticodons and identity elements; [3] these codes are not currently adopted at NCBI, but are numbered here 34-37, and specified in the table below. The standard code
Examples of degeneracy are found in the genetic code, when many different nucleotide sequences encode the same polypeptide; in protein folding, when different polypeptides fold to be structurally and functionally equivalent; in protein functions, when overlapping binding functions and similar catalytic specificities are observed; in metabolism, when multiple, parallel biosynthetic and ...
In the most common variant of sickle-cell disease, the 20th nucleotide of the gene for the beta chain of hemoglobin is altered from the codon GAG to GTG. Thus, the 6th amino acid glutamic acid is substituted by valine —notated as an "E6V" mutation—and the protein is sufficiently altered to cause the sickle-cell disease.
However, in a protein-coding sequence, the DNA sequence is made up of a string of codons which correspond to amino acids. Because the genetic code is degenerate (more than one codon map to a single amino acid) and samples from the amino acids rather than the codons, the codons are not sampled uniformly thus leading to differences in the PCFs.
On the other hand, the codon GAG codes for Glutamic acid while the codon GTG codes for Valine, so a change from the middle A to T does change the resulting protein, for better or (more likely) worse, [b] so the change is not a synonym. These changes are illustrated in the tables below.