helix of Type I collagen is made up of two alpha1 chains and an alpha2 chain encoded by the COL1A1 and COL1A2 genes, respectively. The repetition of glycine, the smallest amino acid, at every third position in the triple helical domain of collagen allows the formation of the triple helix. A change of one base in one of these codons in COL1A1 could cause a missense mutation and the introduction of any one of eight different amino acids at this position. These altered amino acid residues affect the structural properties of collagen, disrupting the extracellular matrix and causing the disease Osteogenesis Imperfecta. The clinical severity of the disease ranges from mild to fatal and correlates with the identity of the amino acid that replaces glycine.
Answer to thought question: Glycine is coded for by four codons: GGU, GGC, GGA, and GGG. A single base substitution in the third base will have no effect on the protein since the codon will still encode glycine. For each of the four codons GGU, GGC, GGA, and GGG we can tabulate the effect of a single base substitution in the first or second base; the unmutated codon is shown in green and the mutated base in red:
| G | G | U | coding for glycine |
| A | G | U | coding for serine |
| U | G | U | coding for cysteine |
| C | G | U | coding for arginine |
| G | A | U | coding for aspartate |
| G | U | U | coding for valine |
| G | C | U | coding for alanine |
| G | G | C | coding for glycine |
| A | G | C | coding for serine |
| U | G | C | coding for cysteine |
| C | G | C | coding for arginine |
| G | A | C | coding for aspartate |
| G | U | C | coding for valine |
| G | C | C | coding for alanine |
| G | G | A | coding for glycine |
| A | G | A | coding for arginine |
| U | G | A | coding for STOP |
| C | G | A | coding for arginine |
| G | A | A | coding for glutamate |
| G | U | A | coding for valine |
| G | C | A | coding for alanine |
| G | G | G | coding for glycine |
| A | G | G | coding for arginine |
| U | G | G | coding for tryptophan |
| C | G | G | coding for arginine |
| G | A | G | coding for glutamate |
| G | U | G | coding for valine |
| G | C | G | coding for alanine |
so the eight possible substituted amino acids are alanine, arginine, aspartate, cysteine, glutamate, serine, tryptophan, and valine.
What other kind of mutation could also arise from a single base substitution of a codon for glycine? The answer is a nonsense mutation since a single base substitution that converts GGA to UGA creates a STOP codon.
SUMMARY
1 DNA, the cell's database, contains the genetic information necessary to encode RNA and protein.
2 The information is stored in the sequence of four bases. These are the purines – guanine and adenine – and the pyrimidines – thymine and cytosine. Each base is attached to the l′‐carbon atom of the sugar deoxyribose. A phosphate group is attached to the 5′‐carbon atom of the sugar. The base + sugar + phosphate is called a nucleotide.
3 The enzyme DNA polymerase joins nucleotides together by forming a phosphodiester bond between the 5′‐phosphate group of one nucleotide and the hydroxyl group on the 3′ carbon of deoxyribose of another. This gives rise to the sugar‐phosphate backbone structure of DNA.
4 The two strands of DNA are held together in an antiparallel double‐helical structure because guanine hydrogen bonds with cytosine and adenine hydrogen bonds with thymine. This means that if the sequence of one strand is known, that of the other can