BIOLOGY 12 MUTATIONS What is a Mutation? A mutation is a permanent change in the DNA sequence of a gene. Mutations in a gene's DNA sequence can alter the amino acid sequence of the protein encoded by the gene. How does this happen? Like words in a sentence, the DNA sequence of each gene determines the amino acid sequence for the protein it encodes. The DNA sequence is interpreted in groups of three nucleotide bases, called codons. Each codon specifies a single amino acid in a protein. Mutate a sentence! We can think about the DNA sequence of a gene as a sentence made up entirely of threeletter words. In the sequence, each three-letter word is a codon, specifying a single amino acid in a protein. Have a look at this sentence: Thesunwashotbuttheoldmandidnotgethishat. If you were to split this sentence into individual three-letter words, you would probably read it like this: The sun was hot but the old man did not get his hat. This sentence represents a gene. Each letter corresponds to a nucleotide base, and each word represents a codon. There are two types of mutations: frameshift and point.

FRAMESHIFT MUTATIONS What if you shifted the three-letter "reading frame?" You would end up with hes unw ash otb utt heo ldm and idn otg eth ish at. Or TTh esu nwa sho tbu tth eol dma ndi dno tge thi sha t. Insertion mutations and deletion mutations add or remove one or more DNA bases. Insertion and deletion mutations cause frameshift mutations, which change the grouping of nucleotide bases into codons. This results in a shift of "reading frame" during protein translation. The proteins are completely nonfunctional.

POINT MUTATIONS: Point mutations are single nucleotide base changes in a gene's DNA sequence. This type of mutation can change the gene's protein product in the following ways: • Missense mutations are point mutations that result in a single amino acid change within the protein. UAC – CAC – this leads to a change in shape of protein and its function. The fat cat. – The rat cat. • Nonsense mutations are point mutations that create a premature "translation stop signal" (or "stop" codon), causing the protein to be shortened. UAC – UAG. The fat cat. – the cat cat. • Silent mutations are point mutations that do not cause amino acid changes within the protein. A silent mutation changes a nucleotide without changing the codon. For many amino acids the third nucleotide of the codon can be variable. For example, CCT, CCC, CCA and CCG all code for Proline. The fat cat. - The fat rat.

What Causes DNA Mutations? Mutations in DNA sequences generally occur through one of two processes: 1.

DNA damage from environmental agents such as ultraviolet light (sunshine), nuclear radiation or certain chemicals called mutagens.

2. Mistakes that occur when a cell copies its DNA (in replication) in preparation for cell division. 1. DNA damage from environmental agents

Modifying nucleotide bases Ultraviolet light, nuclear radiation, and certain chemicals can damage DNA by altering nucleotide bases so that they look like other nucleotide bases.

When the DNA strands are separated and copied, the altered base will pair with an incorrect base and cause a mutation. In the example below a "modified" G now pairs with T, instead of forming a normal pair with C.

Breaking the phosphate backbone Environmental agents such as nuclear radiation can damage DNA by breaking the bonds between oxygens (O) and phosphate groups (P).

Breaking the phosphate backbone of DNA within a gene creates a mutated form of the gene. It is possible that the mutated gene will produce a protein that functions differently. Cells with broken DNA will attempt to fix the broken ends by joining these free ends to other pieces of DNA within the cell. This creates a type of mutation called "translocation." If a translocation breakpoint occurs within or near a gene, that gene's function may be affected.

2. Mistakes created during DNA duplication Prior to cell division, each cell must duplicate its entire DNA sequence. This process is called DNA replication. DNA replication begins when a protein called DNA helicase separates the DNA molecule into two strands.

Next, a protein called DNA polymerase copies each strand of DNA to create two doublestranded DNA molecules.

Mutations result when the DNA polymerase makes a mistake, which happens about once every 100,000,000 bases. Actually, the number of mistakes that remain incorporated into the DNA is even lower than this because cells contain special DNA repair proteins that fix many of the mistakes in the DNA that are caused by mutagens. The repair proteins see which nucleotides are paired incorrectly, and then change the wrong base to the right one.

What are Genetic Disorders? Genetic disorders are medical conditions caused by mutations in a gene or a set of genes. Mutations are changes in the DNA sequence of a gene. They can happen at any time, from when we are a single cell to when we are 90. Or even older! Some people say that there are disorder genes. It is not a gene, or genes, however, that cause the illness, but a mutation that causes the normal genes to operate improperly. It is better to say that there are mutated genes that cause genetic disorders. We can separate genetic disorders into four categories:

1. Chromosome Abnormalities

2. Single-Gene Disorders

In some disorders, entire chromosomes, or large segments of them, are missing, duplicated, or otherwise altered. Down Syndrome and Turner's Syndrome are examples of this type of disorder.

Some disorders result when a mutation causes the protein product of a single gene to be altered or missing. An example of this kind of disorder is sickle cell anemia.

3. Multifactorial Disorders

4. Mitochondrial Disorders

Multifactorial disorders result from mutations in multiple genes, often coupled with environmental causes. The complicated bases of these diseases make them difficult to study and to treat. Heart disorder, diabetes and cancer are examples of this type of disorder.

These relatively rare disorders are caused by mutations in non-chromosomal DNA located within subcellular organelles, the mitochondria. There are multiple copies in a single cell's cytoplasm, all transmitted by the mother in the ovum.

Some mutations cause disorders, but others do not. Why not? Some mutations do not cause disorders because the mutations are repaired. Our cells have mechanisms for repairing DNA if mistakes are made in the sequence or if the DNA is damaged. We have two copies of every chromosome (one from Mom and one from Dad), and therefore we have two copies of every gene. If one gene copy is mutant, the other copy usually can provide enough gene product to the organism for normal function. Most of our DNA does not encode genes. Therefore most mutations do not cause changes in functional gene products, and do not cause genetic disorders. Even among the DNA sequences that serve as blueprints for gene products, many changes in the DNA do not cause significant changes in the protein sequence translated from that DNA, and therefore cause no detriment to the organism.