 In this video, I will define mutation and explain how the following mutations may affect the final protein, silent mutations, point mutations, or frame shift mutations. A mutation is a change in the nucleotide sequence of a gene. A mutation could result from a mistake during DNA replication, or could be a result of an environmental factor known as a mutagen. There are a variety of chemicals that are mutagens that could cause a change in the DNA sequence. Also, extreme UV light exposure from intense sunlight can damage the DNA and is another example of a mutagen. A silent mutation is a mutation that does not affect the sequence of amino acids in the resulting protein and therefore won't affect the function of the protein. A silent mutation is still a change in the nucleotide sequence of a gene, but it has no real consequence to the protein. Point mutations, which are also known as substitutions, are a change in a single nucleotide within a DNA sequence. The example of a silent mutation that we see in this illustration is a point mutation where the cytosine is replaced with thymine, producing a codon that also codes for the amino acid lysine. A nonsense mutation is a mutation that converts a codon for an amino acid into a stop codon. This will disrupt translation, producing a shortened version of a polypeptide, a truncated polypeptide. The example of a nonsense mutation we see here is a type of point mutation where the first thymine in the codon was changed to an adenine. Now the resulting messenger RNA contains a stop codon, UAG, therefore the resulting polypeptide will be stopped once that codon is reached. Typically a nonsense mutation will have a severe effect on the function of a protein. A missense mutation is a type of mutation where a codon for one amino acid changes to a codon for a different amino acid. We see two examples here of point mutations which are missense mutations. The first is a conservative missense mutation where the amino acid lysine is changed with the amino acid arginine. Lysine and arginine are both cationic side chains, that is they both have a positive charge. Lysine and arginine will have a similar function for the resulting polypeptide. The overall structure of the polypeptide as it folds will be very similar. The function of the protein that results from a conservative missense mutation will either not be affected at all or it will only have a minor effect on its function. A non-conservative missense mutation will replace an amino acid for a different amino acid that will have a significant effect on the structure and function of the resulting protein. The example we see here, threonine replaces lysine and threonine is not a positively charged amino acid. Therefore the resulting structure of the protein would change and it's likely that the protein's function would be significantly disrupted. While mutations are often bad, disrupting the function of proteins could potentially lead to disruption of the cell's function. It could kill the cell or cause the cell to start dividing in an uncontrolled way which might cause cancer. However some mutations create new functions that are helpful and this process of mutation is what enables the rich diversity of life in our planet and has enabled the mechanism of evolution by natural selection to produce the diversity of species that are alive today, all descending from a common ancestor. Sickle cell anemia is an example of a point mutation that is a non-conservative missense mutation. The change in the DNA sequence of a codon CTT to CAT results in a change in the codon of the messenger RNA from GAA to GUA. GAA codes for the amino acid glutamate and glutamate is a polar amino acid whereas GUA codes for the amino acid valine and valine is a non-polar hydrophobic amino acid. This change in the primary structure of the protein has an effect on the secondary tertiary structures of the resulting hemoglobin protein which causes hemoglobin to clump forming fibrous strands within erythrocytes and the resulting erythrocytes then become sickle shaped, clumping together more easily, breaking more easily and blocking the flow of blood through the blood vessels leading to the symptoms of anemia from a low oxygen carrying capacity of the blood as well as other symptoms of sickle cell disease which result from disruption of blood flow through small vessels. While sickle cell disease has many negative health consequences it is also an example of how a mutation can produce an advantage. Sickle cell anemia does have an advantage. Sickle cell anemia protects people from malaria and this is why sickle cell disease is much more common in black people because this mutation protected people against the malaria that is prevalent in tropical regions of Africa. Another type of mutation that is not a point mutation is known as a frameshift mutation. A frameshift mutation occurs when nucleotides are inserted or deleted from a gene sequence and if those nucleotides are inserted and deleted as either one or two, four, five, anything that is not a multiple of three will result in throwing off the reading frame for the ribosome during translation. Therefore a frameshift mutation will typically have a drastic effect on the resulting polypeptide and disrupt the function of the protein. The example that we see here the nucleotides U and A were deleted from the codon for valine. As a result the codon changes at that position to GCC and so instead of valine and alanine is inserted during translation but notice the next amino acid is not proline now it's lucine and then instead of tyrosine another lucine and this is because the reading frame changed as a result of a frameshift mutation and all of the resulting codons will be affected. All of the codons that are downstream from the frameshift mutation will be affected. This could lead to a premature stop codon producing a shorter polypeptide and it's also likely to produce numerous missense mutations where the codons have been changed as a result of shifting the reading frame by one or two bases.