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Errors in the Code Slide 2 Mutations are not just the stuff of science fiction movies. Mutations happen every day in all kinds of cells in all kinds of organisms. A mutation is a change in an organism’s DNA that can be passed on to other cells or offspring. There are many different kinds of mutations that are categorized by where they occur. We will look at somatic and germ-line mutations, point and chromosomal mutations, and spontaneous and induced mutations. Slide 3 In a single-celled organism any change in the DNA will be passed on to its “offspring” when the cell divides and gives rise to two new cells because each daughter cell receives an exact copy of the DNA. For multicellular organisms two different types of mutations may arise. Somatic mutations occur when the DNA in a non-gamete cell is altered. These mutations are passed on to daughter cells when the original cell divides during mitosis. Somatic mutations may adversely affect the organism, but cannot be passed on to the organism’s offspring. Skin cancer is an example of a somatic mutation. Germ-line mutations are found in gametes or cells that give rise to gametes. These mutations can be passed on to offspring, but do not adversely affect the parent. Down Syndrome, when a gamete receives three copies of chromosome 21, is an example of a germ-line mutation. Slide 4 Point mutations involve an alteration of a single base in a DNA molecule. The first of the 4 types of point mutations is called a silent (or synonymous) mutation. Recall that the genetic code is redundant, that is, there may be more than one codon that codes for a specific amino acid. For example there are four codons for leucine, two codons for glutamic acid, three stop codons, and so on. A silent mutation is one in which a base is changed, but the resulting mRNA still codes for the same amino acid. These mutations have no adverse effects on the organism because the correct protein is still synthesized. Silent mutations are very useful in phylogenetics as we will see later in the course. Slide 5 Missense mutations occur when a base in the DNA is changed, resulting in a codon for a different amino acid. The resulting polypeptide has one incorrect amino acid in its sequence. These mutations usually have consequences for the organism because the resulting protein may not have the correct shape and therefore may not function correctly. In many cases missense mutations cause a protein to function less efficiently than the correctly formed protein, so an organism may be able to survive with this type of mutation. Sickle cell disease is an example of a missense mutation . Slide 6 Nonsense mutations have more serious consequences for an organism. In nonsense mutations, a base is changed such that a stop codon is inserted into the mRNA sequence. Translation terminates prematurely, leaving a truncated polypeptide sequence that may not form a functional protein. The organism may be left without a protein that is essential to life. Slide 7 Frame-shift mutations involve the insertion or deletion of a base in the DNA sequence. Remember that codons are like a series of 3-letter words. Inserting an extra letter in or deleting a letter from the sequence will move all of the other letters over one, but the translation machinery is still going to read the sequence three letters at a time. All of the codons after the insertion will code for different amino acids, and the resulting polypeptide sequence will essentially be random. This type of mutation also has serious consequences for the organism because essential proteins may not by synthesized. Slide 8 There are also 4 types of chromosomal mutations – mutations that involve pieces of a chromosome rather than just a single base. A deletion is exactly what it sounds like – part of the chromosome breaks into two pieces; a segment of the chromosome is lost, and the remaining pieces join together. This type of mutation can have consequences similar to those arising from a frame-shift mutation. The 3-letter codons will be out of register and will code for the wrong amino acid sequence. Slide 9 When a chunk of a chromosome gets deleted, as in the last slide, what happens to it? When homologous chromosomes break at different points and reconnect with the wrong partners as in this example, one chromosome ends up with a deletion while the other has a duplication. Slide 10 Sometimes a deleted piece of a chromosome will be flipped over before it is reinserted into the chromosome. Now part of the genetic code is running in the opposite direction. Any resulting protein would be seriously altered and probably nonfunctional. This type of mutation is called an inversion. Slide 11 That broken piece of chromosome may meet another fate. When a segment of chromosome breaks off one chromosome and is reinserted into a different chromosome, translocation has occurred. The example here shows a reciprocal translocation. Non-homologous chromosomes have exchanged segments. This type of mutation can cause problems during meiosis. Slide 12 How do all these types of mutations arise? Spontaneous mutations occur because DNA replication, while extremely accurate, is not perfect. Instability in the chemical structures of the nucleotide bases can lead to errors in base pairing during DNA replication. Although proofreading catches most of these errors, some slip by. Chromosome breakage leading to translocations and inversions can occur during meiosis also, giving rise to germ-line mutations. Mutations may be induced, that is, they may be caused by some environmental factor that alters the DNA. It is pretty common to hear that certain chemicals are carcinogenic. Usually the reason they are carcinogenic is that they are also mutagenic or mutationcausing. These types of chemicals may alter the base pairing properties of the nucleotide bases or interfere with a base’s ability to pair at all. Different types of radiation, such as X-rays and ultraviolet radiation, are well-known mutagens and are sometimes used in genetic experiments to induce mutations. Slide 13 Mutations are occurring inside our bodies every day. The frequency of mutations in DNA replication is about 1 mutation in 104 base pairs, but proofreading and repair reduce that frequency to about 1 mutation in 109 base pairs. Still, with all the cells in our bodies and the rate at which they divide, at least during some parts of our lives, that seems like a lot of mutations. Why aren’t we all X-men? Remember that we have an enormous amount of DNA in each of our cells, but not all of it contains genes that are expressed. Some parts of our DNA simply don’t contain genes while other parts may contain genes that aren’t switched on. Mutations, being random, often occur in the parts of our DNA that don’t contain genes. Also, due to the redundancy in the genetic code, many mutations are silent and don’t affect protein synthesis. Mutations are important in evolution because they provide genetic variability on which natural selection can act. Remember that mutations are random – some are advantageous, many are neutral, but many are harmful to an organism. Harmful mutations are usually lethal and less likely to be passed on to the next generation. If the mutation provides an advantage for the organism it can be passed on to subsequent generations, eventually becoming part of the gene pool for the species. Natural selection, however, is not random and selects the individuals best suited to their environment.