Substitution Mutations Involved in Sickle Cell Anemia
Simply defined, a mutation is merely a change in the DNA. Within a cell, DNA molecules are not absolutely stable, and each base pair within a DNA strand has some probability of mutating (Griffiths et al. 452). Mutations that occur within an individual gene are known as gene mutations, and they are classified into two types: induced and spontaneous. Induced mutations are those that occur with exposure to some type of mutagen, while spontaneous mutations arise in the absence of any mutagen (Griffiths et al. 453). The mutations in these categories can be point mutations, where a single nucleotide base in the DNA is either substituted for another base, or there is an addition or deletion of an entire base pair (Griffiths et al. 454). Mutations may also arise as simultaneous additions and deletions of multiple base pairs at once (Griffiths et al. 454). If these mutations occur within a protein-encoding gene, they can have deleterious consequences. In fact, several human diseases are caused by such point mutations.
A disease that is commonly used to illustrate the effect of mutation is sickle cell anemia. In sickle cell anemia, a single nucleotide substitution is made: CTC to CAC (Berg, Tymoczko, Stryer 209). When transcribed into mRNA, this substitution becomes a GUG codon, which codes for the amino acid valine instead of the normal amino acid glutamate (Berg, Tymoczko, Stryer 209). This change in amino acid in the β-hemoglobin chain has negative consequences because when the hemoglobin is in a deoxygenated state, the hydrophobic valine residue can interact with a hydrophobic patch that is exposed, causing to molecules to aggregate (Berg, Tymoczko, Stryer 209).
Berg, Jeremy M., John L. Tymoczko, and Lubert Stryer. Biochemistry. 7th ed. New York: W.H. Freeman, 2012. Print.
Griffiths, Anthony J. F., Richard Charles. Lewontin, Susan R. Wessler, and Sean B. Carroll. Introduction to Genetic Analysis. 9th ed. New York: W. H. Freeman, 2008. Print.