Chapter 7 Gene Experssion and Control Part 3
Mutated Genes and Their Products • Mutations are changes in the sequence of a cell’s DNA. • If a mutation changes the genetic instructions for building a protein, an altered polypeptide product will result. • Since the genetic code is a degenerate code, a change in the sequence of the DNA does not have to code for an altered polypeptide. • For example, a mutation that changes UCU to UCC will still code for the amino acid serine. Therefore, there will be no change in the polypeptide product. • A mutation like this is called a silent mutation since it does not affect the amino acid sequence of the polypeptide that is produced from the gene. • However, there are other mutations that have drastic effects.
Mutated Genes and Their Products • A mutation in the hemoglobin molecule can provide us with such an example. • A red blood cell carries oxygen molecules bound to hemoglobin molecules. As these cells circulate through the lungs, the hemoglobin proteins bind oxygen gas, then give it up in the tissues. The the red blood cells return to the lungs where their hemoglobin can pick up more oxygen. • The hemoglobin protein can only bind oxygen because of its structure. It is made of four polypeptide chains (called globins). Each chain folds around a heme group, which is a cofactor with an iron atom at its center. Oxygen binds to hemoglobin at these iron atoms. • In adults, each hemoglobin molecule is made up of two alpha globin chains and two beta globin chains. • Defects in these chains can cause a condition known as anemia, in which a person’s blood is deficient in red blood cells or in hemoglobin. Either way, this limits the blood’s ability to carry oxygen.
Mutated Genes and Their Products • A deletion mutation is a mutation in which one or more nucleotides are lost from the DNA. • The loss of a particular nucleotide from one of the beta globin chains causes beta thalassemia, which is a type of anemia. • A deletion is a frame shift mutation since it causes the reading frame of mRNA codons to shift. • This shift messes up the genetic message as in the example below: • Normal Message: The fat cat ate the rat. • Deletion occurs (T deleted): hefatcatatet her at.
Mutated Genes and their products • An insertion or addition mutation occurs when extra bases become inserted or added into the DNA. • Like a deletion, insertion/addition mutation are frame shift mutations since they also cause the reading frame of mRNA codons to shift. • Example: • Normal message: The fat cat ate the rat. • Insertion occurs (Another T added): TThefatca tat eth era t.
Mutated genes and their products • With a base-pair substitution mutation, a nucleotide and its partner are replaced by a different base pair. • This can result in an amino acid change or a premature stop codon in the mRNA. • Sickle cell anemia is a result of a substitution mutation. • These mutations are called missense mutations. Since they do not shift the reading frame, they do not totally change the message, but they may cause the message to be slightly different if the amino acid is changed as a result of the mutation. • Example: • Normal message: The fat cat ate the rat. • Sustitution occurs (r substituted for c): The fat rat ate the bat.
The hemoglobin mutation • Specifically, a substitution in the DNA causes the sixth amino acid to of the beta globin chain to be valine instead of glutamic acid. • Glutamic acid carries a negative charge, but valine has no charge. This causes a tiny patch of the beta globin chain to change from hydrophuillic to hydrophobic, which in turn causes the structure and behavior of the hemoglobin molecule to change slightly. • This causes the hemoglobin molecules to stick together and form large, rod-like clumps. This causes the shape of the red blood cell to change from concave to crescent shaped. • These crescent-shaped red blood cells clog tiny blood vessels, which in turn disrupts blood circulation throughout the body. • Over time, this can damage organs and even cause death.
The Hemoglobin mutation Normal Red Blood Cell Sickle Cell Anemia
What causes mutations? • Insertion/addition mutations are often caused by what are called transposable elements. • Transposable elements are segments of DNA that can insert themselves anywhere in a chromosome. • Certain kinds of transposable elements can spontaneously move themselves from one place to another within the same chromosome or to another chromosome entirely. • These segments of DNA can be hundreds to thousands of base pairs long, so when one is inserted into the DNA into a particular location, in can become a major insertion that totally changes the gene’s product. • These elements occur in the DNA of all species and about 45% of human DNA consists of transposable elements or their remnants.
What causes mutations? • Many mutations occur spontaneously during DNA replication, which is not surprising since DNA replication occurs so quickly (about 20 bases per second in humans and about 1000 bases per second in bacteria). • Even though DNA polymerases make mistakes at predictable rates, most of the time, they correct their mistakes. However, as we discussed previously, when they don’t, their mistake becomes a mutation.
What causes mutations? • Harmful environmental agents also cause mutations. • High energy waves such as Xrays can ionize atoms (kick their electrons out). This can cause chromosomes to break into pieces that then get lost during DNA replication. • Ionizing radiation can also indirectly damage DNA because it leaves a trail of destructive free radicals when it penetrates living tissue. These free radicals also damage DNA.
What causes mutations? • Nonionizing radiation such as UV rays can boost electrons to higher energy levels, causing adjacent bases to covalently bond to one another. • The resulting dimer causes a kink in the DNA. • This kink can cause DNA polymerase to copy the kinked part incorrectly, so a mutation gets introduced into the DNA. • Many mutations that cause cancer begin with thymine dimers (two adjacent thymines covalently bonded together). • Exposing unprotected skin to sunlight increases the risk of skin cancer because it causes thymine dimers to form in the DNA of skin cells.
What causes mutations? • Some natural or synthetic chemicals can also cause mutations. • Chemicals in cigarette smoke transfer small hydrocarbon groups to DNA nitrogen bases. • These altered bases may mispair during DNA replication, or stop replication completely. • Both of these things increase chances of mutations.