DNA Mutations Remember that during DNA replication the

DNA Mutations

• Remember that during DNA replication, the DNA makes an exact copy of itself before it divides. • DNA replication is not always accurate. • sometimes the bases get copied wrong in the new strand of DNA causing a permanent change or mutation.

• Mutation: A permanent change in the sequence of DNA. • Mutations can cause the protein to be made incorrectly. • If the protein is made incorrectly, it will not function correctly • Sometimes it will not function at all.

There are two main types of mutations based on the size of the mutation. 1. Point mutations 2. Chromosomal mutations.

1. Point Mutations is a mutations involving one nucleotide (base) in a gene • Sometimes several are involved.

Point mutations are subdivided into groups a. Substitution b. Silent mutation c. Deletion d. insertion

a. Substitution: occurs when one base is substituted for another during replication. Picture the normal DNA code being a sentence: THE DOG BIT THE CAT A substitution would look like this: THE DOG BIT THE CAR The “T” in CAT was substituted with an “R” to make a new word and give the sentence new meaning.

Actual substitution: seventh base, the “G” was substituted for an “A” during replication. Normal code AUG UUG GGC GGA UUG UAA Met Phe Gly Leu Stop Mutated code AUG UUG AGC GGA UUG UAA Met Phe Ser Gly Leu Stop

Normal code AUG UUG GGC GGA UUG UAA Met Phe Gly Leu Stop Mutated code AUG UUG AGC GGA UUG UAA Met Phe Ser Gly Leu Stop • Notice that only one amino acid has been changed • because one codon on m. RNA was changed.

Making Proteins DNA: DNA TAC CGA TCG TGA ACT Transcription m. RNA: AUG GCU AGC ACU UGA Translation Protein: Met-Ala-Ser-Thr-Stop

Effect of Mutation on Protein DNA: DNA TAC CGA TCG C TGA ACT Transcription m. RNA: AUG GCU G AGC ACU UGA Translation Protein: Met-Ala-Ser-Thr-Stop Gly

• Sickle cell anemia is disease caused by a substitution point mutation • The gene that codes for the hemoglobin protein on red blood cells is made incorrectly. Normal red blood cell Sickle cell red blood cell

• In this gene, just one base is changed • causes one amino acid difference in the hemoglobin protein. • causes the protein to fold differently and not function properly in carrying oxygen in the bloodstream. VAL was substituted for GLU causing the cell to sickle

b. Silent mutation: a substitution where the mutated DNA codes for the same amino acid as the original DNA. Example: THE DOG BIT THE CAT 1. Change the sixth letter “G” to a “g” A mutation would look like this THE DOg BIT THE CAT The sentence is the same with the same meaning so the mutation had no effect.

Normal DNA code AUG UUG GGC GGA UUG UAA Met Phe Gly Leu Stop 1. Substitute the sixth base to A Mutated DNA code AUG UUA AGC GGA UUG UAA Met Phe Gly Leu Stop

Normal DNA code AUG UUG GGC GGA UUG UAA Met Phe Gly Leu Stop Mutated DNA code AUG UUA AGC GGA UUG UAA Met Phe Gly Leu Stop • Both UUG and UUA code for Phe. Does not change the protein thus called a silent mutation.

c. Deletion: single nucleotide (base) is deleted from the DNA Example: THE DOG BIT THE CAT 1. Delete the sixth letter “G” THE DO_ BIT THE CAT 2. The words must be read in groups of three like codons 3. Every letter shifts to the left After the deletion and shift of letters THE DOB ITT HEC AR

Example: THE DOG BIT THE CAT After the deletion THE DOB ITT HEC AR • Notice that a deletion causes every letter to shift to the left • It must be read in 3’s • This changes every word after the deletion, • Changes the entire sentence making it meaningless.

Normal DNA code AUG UUG GGC GGA UUG UAA Met Phe Gly Leu Stop 1. The eighth base gets deleted. “G” 2. Shifts the entire code to the left. Mutated DNA code with deletion AUG UUG GCG GAU UGU AA Met Phe Ala Val Cys

Normal DNA code AUG UUG GGC GGA UUG UAA Met Phe Gly Leu Stop Mutated DNA code with deletion AUG UUG GCG GAU UGU AA Met Phe Ala Asp Cys • Notice that every amino acid after the deletion had changed • This protein has problems. • May not work correctly if at all.

d. insertion: single nucleotide (base) is inserted into the DNA. Example: THE DOG BIT THE CAT 1. Insert a “G” after the word THE After the insertion THE GDO GBI TTH ECA T 2. Every word after the insertion is changed and the sentence has no meaning

Normal DNA code AUG UUG GGC GGA UUG UAA Met Phe Gly Leu Stop 1. Insert a “C” after the sixth base 2. Shifts the entire code to the right Mutated DNA, insertion AUG UUG CGG AUU GUA A Met Phe Arg Ile Val

Normal DNA code AUG UUG GGC GGA UUG UAA Met Phe Gly Leu Stop Mutated DNA, insertion AUG UUG CGG AUU GUA A Met Phe Arg Ile Val • Notice that every amino acid after the deletion had changed • This protein too has problems. • May not work correctly if at all.

Insertions and deletions are known as frameshift mutations. Frameshift mutation: the insertion or deletion causes a shift in the reading frame of the DNA • Deletions cause the bases to shift to the left • Insertions cause the bases to shift to the right • Every amino acid after the insertion or deletion is changed • This changes the entire polypeptide chain.

Gene Mutations: Substitution, Insertion, and Deletion (frameshift mutations) Substitution Go to Section: Insertion Deletion

Chromosomal Mutations • Chromosomal mutations: involve changes in the number or structure of chromosomes. – Changes may include: – locations of genes on chromosomes, – number of copies of genes.

Four types of chromosomal mutations 1. deletion: 2. duplication: 3. inversion: 4. translocation: Down syndrome: 47 chromosomes

1. deletion: loss of all or part of a chromosome.

2. duplication: segment of the chromosome is repeated.

3. inversion: part of the chromosome gets flipped around and reattached.

4. translocation: part of one chromosome breaks off and attaches to another chromosome.

• How do mutations happen? • Many mutations are not caused by errors in replication. • Mutations can be caused by mutagens • Mutagen: something in the environment that causes a mutation

Examples of mutagens a. Ultraviolet or solar radiation (sun) b. nuclear radiation c. Cigarette smoke d. X-rays e. chemicals in the environment There are many more

Mutations often lead to problems including • cancer • birth defects and • proteins or enzymes that do not work like sickle cell anemia.

• In rare cases, the mutation can be beneficial. • For example, mutation cause the loss of an enzyme that makes a moth a lighter color. • That moth has an advantage in light environments. • So in this case, the mutation was beneficial.

• Mutations are the driving force behind evolution. • Over millions of years, mutations can accumulate causes big changes and the creation of new species.

Important: • In order for mutations to be passed to the next generation, they must be in sex cells. • That includes sperm and eggs. • You cannot pass on mutations if they occur in the lungs or heart.